How many times was the variation represented by rs8137714 observed? What population and how many chromosomes did you screen?

Currently, rs8137714 does not have genotype or allele frequency information in dbSNP. To see how the submitted SNPs in this refSNP cluster were mined, do the following:

1.

Go to the refSNP report for rs8137714 and look at the “Submitter Records” section

2.

Click on either of the NCBI Assay ID numbers located on the left. This will take you to the submitted SNP Detail report for the selected SNP.

3.

Scroll down to the Assay section of the Detail Report, and click on the assay “Method” listed there. This will take you to a description of the method used for finding the submitted SNP.

By following the above steps, you can see that both submitted SNPs in this cluster were computationally mined.

If you look at the Validation Summary” section located at the bottom of the refSNP report, you will see that this SNP is a “Double Hit” SNP. In other words, “all alleles have been observed in at least two chromosomes apiece.” You can find more information on Double hit SNPs in the dbSNP FAQ Archive.

Some submitters will submit frequency information for existing refSNP numbers, so it is possible that dbSNP will get frequency information for this refSNP (rs) number in the future. (11/26/07)

The reported frequency of a minor variant is GCGATTGGCC{G/A}GGACCACGAC 0.102 plus/minus 0.012. Can I assume that the minor variant is A?

When a SNP is submitted as (G/A), we do not assume that the "G" allele is the major (wild-type) variant, and the “A” allele is the minor variant. Because the minor allele in one population can be the major allele in an other population, we do not assume allele order implies allele frequency information, and do not interpret the data at all — to bdSNP, both the "G" variant and the "A" variant have been observed at the SNP location, and that is all.

At the same time, however, we have been, and will continue to encourage dbSNP users to submit individual genotype data or genotype/allele frequency data for both new and existing SNPs. Once we have allele frequency data, we can then state the minor allele and its frequency. (5/1/06)

How do I determine orientation of a SNP allele (rs9934438) in dbSNP, and then find the corresponding strand and position information in the UCSC genome browser?

To find orientation information about a SNP, go to the “Integrated Maps” section of the SNP’s cluster report. In the case of rs9934438, you can see that rs9934438 hits on the plus strand of NT_010393.15 in the reference assembly. rs9934438 has allele “A/G” (see the “allele” section at the top of the page) and the contig allele of NT_010393.15 is “G” at the SNP position.

To find the link to UCSC’s genome browser for this refSNP, click on "Links" (located just to the right of the “Alleles” section at the top of the refSNP page) and choose “UC Santa Cruz” to go to the UCSC browser at the location of this particular SNP. As of this date, B129 is the most recent.

(09/12/08)

dbSNP reports rs10512248 alleles as A/C, but Nature Genetics 40(5):pp.575 table 1 reports rs10512248 as G/T, where “alleles all refer to the positive strand.”

I think the "positive strand" mentioned in this paper refers to the NCBI reference assembly strand.

rs10512248 maps to the NCBI reference sequence on the minus strand (see the integrated maps section of the cluster report). That is why dbSNP shows the rs allele as reversed to what the paper reports. In other words, SNP alleles can be described as either in "RefSNP orientation" or in "reference genome strand orientation". If you take the orientation of both the refSNP and the genome into consideration, then the data from dbSNP and the data in the paper are consistent.

Here are a couple of reasons dbSNP does not report alleles in genome orientation:

• dbSNP maps refSNPs to several alternative assemblies (Celera, HuRef) as well as to the reference assembly, and sometimes these different assemblies are in different orientations at the SNP position.
• Some SNPs do not map to any genome positions or they may have multiple positions, making it impossible to report the refSNP allele in genome orientation.

I would also like to point out that a refSNP never changes orientation between dbSNP builds. And if we assume genome sequences do not change strand orientation (which is, for the most part, true), then if a refSNP maps to the minus strand of build 35, then it will also map to minus strand in build 36, and to the minus strand in other future builds.(08/06/08)

Will refSNP flanks change orientation between builds?

A refSNP’s flanking sequence will never change orientation, but a refSNP’s orientation with respect to the genome may change between builds if the genome assembly itself has significant changes that occur between builds. This was the case in the earlier human genome builds, but the human genome build is more stable now, so orientation changes such as this will occur less often.

There are several different orientation types which exist in dbSNP:

• The orientation of a submitted SNP(ss) flank with respect to the RefSNP cluster (rs) flank.
• The orientation of the rs flank with respect to the contig sequence.
• The orientation of the contig sequence with respect to the genome.
  Please note that all placed human contigs are in the same orientation as genome.
• The orientation of a refSNP with respect to the genome.
  Since all placed contigs have the same orientation as genome, this orientation is the same as rs orientation to contig in human.
• The orientation of an mRNA with respect to the contig.
  This might not be related to our discussion here, but I mention it since it might come up in another context.

We make sure that a refSNP’s flanking sequence orientation never changes: If a new ss is added to a refSNP cluster, and if that new ss has the longest flanking sequence (and therefore becomes the exemplar of the cluster), but has reverse orientation with respect to the existing rs, we reverse its flanking sequence when it becomes the new rs flank. (11/20/07)

I am interested in retrieving flanking sequences in the forward orientation for a list of b126 SNPs. How do I do this?

A refSNP (rs) flanking sequence is simply the flanking sequence of the longest submitted SNP (ss) in the refSNP cluster. The ss with the longest flanking sequence is called the "refSNP exemplar". If a refSNP cluster gets a new ss member added after build 126 and this new ss has flanking sequence that is longer than the flanking sequences of the existing ss in the cluster, then the new ss becomes the refSNP cluster’s exemplar, its flanking sequence is adjusted for orientation, and it will be used as the rs cluster’s flanking sequence in the next build. Since the new ss will, in most cases, align at the same position as the rs, the flanking sequence difference should be small. I am therefore curious why you want would need the rs flanking sequence for build 126. Have you noticed a significant difference (other than length) between rs flanks in different builds?

In general, dbSNP does not keep old build data due to data size issues and the complexity of tracking assembly changes between builds. However, if you have a local copy of dbSNP, you can access the rs flanking sequence for a particular build since dbSNP keeps the flanking sequences of all submitted SNPs. If you do not have a local copy of dbSNP that you can query, give us a list of the rs numbers in question, we can pull the data for you.(11/20/07)

In the refSNP report for rs1805794, does the allele notation “C/G” mean that C is on the forward strand of the chromosome in the reference assembly (and the variation is C/G)?

Alleles as shown in the RefSNP report are in the order dictated by the ascii character set. C/G, therefore, does not imply that the C is on the forward strand of chromosome in reference assembly. The "Integrated Mapping" section of the report shows the contig allele and orientation. In this case, the contig allele is "C" on the reference assembly, and it is in the same orientation as the SNP flanking sequence. (5/4/06)

How do I find the set of alleles that you used to instantiate a SNP allele sequence?

We do not choose the alleles for a SNP. We include all alleles reported by submitters for a refSNP cluster. If a submitted SNP is on the reverse strand relative to the refSNP sequence, we reverse the alleles. For example, in the refSNP(rs) cluster rs268, rs268and ss268 have the allele A/G, while ss48420135 shows the C/T allele on the reverse strand. So the reported allele set for refSNP cluster rs268 is reported as A/G.

(6/21/06)

Are the M, Y, R, W, K and S codes you use in the FASTA sequence at the SNP position designed by American Association of Biochemistry?

Yes. We use IUPAC codes in FASTA sequences at the SNP position. You can find the IUPAC code in many websites. Here is an example of one such listing.(07/22/08)

In one place, the report for rs6993291 shows the variant allele as M, and then elsewhere in the report it says the variant allele is A/C. Which is it? What does M stand for?

In some cases the report may display the IUPAC ambiguity code equivalent of the variant allele rather than displaying the variant allele itself (e.g. M = A/C). (3/7/06)

The variation position notation for rs1922237 is: “12382526^12382527”. What does this notation mean?

In this case, the contig has a deletion at the SNP position and actually has a new "allele" (a deletion) that was not reported by the submitters to dbSNP.

When a contig has a deletion at a SNP position, it does not necessarily mean that the SNP is a DIP (Deletion Insertion Polymorphisim), since dbSNP does not always have an exhaustive list of variation alleles for each SNP.

The SNP to contig positions in SNP builds so far have three loc_type(s), each of which has a specific notation:

• loc_type 1, where the contig has multiple bases. The range for loc_type 1 is: “asn-from < asn-to”, which is written as "asn-from..asn-to".
• loc_type 2, where the contig has exactly one base. The range for loc_type 2 is: exact, where “asn-from = asn-to”, and is written as "asn-from"
• loc_type 3, where the contig has a deletion. The range for loc_type 3 is: between, where “asn-to = asn-from+1”, and is written as "asn-from^asn-to”. This loc_type does not depend on the SNP variation class, whether it is a true SNP or a DIP. (9/19/05)

The variation position notation for rs10600037 is: “DIP(+) seq 12489885..12489886”. What does this notation mean?

If there are multiple bases at a SNP position on the contig, then ".." is used to show the location of the variation. In this example, rs10600037 has the deletion insertion polymorphisim (DIP)” —/TG, where the two bases "TG" align at the SNP variation position: 12489885..12489886 on the contig.

The SNP to contig positions in SNP builds so far have three loc_type(s), each of which has a specific notation:

• loc_type 1, where the contig has multiple bases. The range for loc_type 1 is: “asn-from < asn-to”, which is written as "asn-from..asn-to".
• loc_type 2, where the contig has exactly one base. The range for loc_type 2 is: exact, where “asn-from = asn-to”, and is written as "asn-from"
• loc_type 3, where the contig has a deletion. The range for loc_type 3 is:
  between, where “asn-to = asn-from+1”, and is written as "asn-from^asn-to”. This loc_type does not depend on the SNP variation class, whether it is a true SNP or a DIP. (9/19/05)

The variation position notation for rs10532925 is: “DIP(+) seq 86843313”, but this notation does not have the “^”or “..” I’ve seen in the variation position notation for other refSNPs. What does this notation mean?

When there is one base at the SNP position on the contig, then just the base position is listed. rs10532925 has the deletion insertion polymorphisim (DIP)”—/AAA, but the contig allele is "A". So this is a case of the contig showing a new allele for the SNP.

The SNP to contig positions in SNP builds so far have three loc_type(s), each of which has a specific notation:

• loc_type 1, where the contig has multiple bases. The range for loc_type 1 is: “asn-from < asn-to”, which is written as "asn-from..asn-to".
• loc_type 2, where the contig has exactly one base. The range for loc_type 2 is: exact, where “asn-from = asn-to”, and is written as "asn-from"
• loc_type 3, where the contig has a deletion. The range for loc_type 3 is:
  between, where “asn-to = asn-from+1”, and is written as "asn-from^asn-to”. This loc_type does not depend on the SNP variation class, whether it is a true SNP or a DIP. (9/19/05)

The variation position notation for rs4148752 is: “DIP(-) seq 12376835^12376836”. What does this notation mean?

rs4148752 has the deletion insertion polymorphisim: “—/AAAG”, where the contig has the deletion [thus, “DIP(-)”]

The SNP to contig positions in SNP builds so far have three loc_type(s), each of which has a specific notation:

• loc_type 1, where the contig has multiple bases. The range for loc_type 1 is: “asn-from < asn-to”, which is written as "asn-from..asn-to".
• loc_type 2, where the contig has exactly one base. The range for loc_type 2 is: exact, where “asn-from = asn-to”, and is written as "asn-from"
• loc_type 3, where the contig has a deletion. The range for loc_type 3 is:
  between, where “asn-to = asn-from+1”, and is written as "asn-from^asn-to”. This loc_type does not depend on the SNP variation class, whether it is a true SNP or a DIP. (9/19/05)

In the Population Diversity section of a refSNP page, what is the definition of “IG” as a “Source” in the Sample Ascertainment section?

IG stands for "Individual Genotype". This means that dbSNP has the actual genotypes, not just the frequencies. (7/19/07)

What is the definition of the population described in a SNP report?

A "population" is submitted and defined by a submitter, which means that the submitter provides a population ID (an abbreviation) as well as a description of the population, therefore, “populations” are not curated by dbSNP.

Please note that genotype data also have populations, but the "population with frequency data" designation is only for populations that have allele frequency submissions, and these do not include genotype submissions.

You can see how major contributors to dbSNP define their populations by going to the “Search/View Population Detail” page and type in the submitter handles "Perelgen" and "CSHL-HapMap" in the search text box located in the grey search section and clicking the “Search” box directly below. (3/9/05)

The report for rs1079610 shows an assay sample size of 65, whereas one of the ss reports for this cluster shows a 2N sample size of 1476. Why are the sample sizes different?

There are two sample-size fields in dbSNP. One field is called the SNP Assay sample size; it reports the number of chromosomes in the sample used to initially ascertain or discover the variation. The other sample-size field is called SNPPOPUSE or population sample size; it reports the number of chromosomes used as the denominator in computing estimates of allele frequencies by dbSNP submitters. These two measures need not be the same.

In this case, the assay sample size for the refSNP is simply the addition of the sample sizes for each member ss. In this case: 48 (from YUSUKE) + 10 (from TSC) + 3 (from SC_JCM) + 2 (from SC_SNP) + 2 (from SSAHASNP) = 65. If multiple ss from the same submitter are in the same cluster, dbSNP counts the sample size only once for each submitter.

The population sample size of 1476 is the sample size reported with the population frequency data in ss4926339, reported by YUSUKE.

The refSNP report for rs7735338, shows that there are 120 samples for the European population. Does this mean that the sample is 120 CEPH cell lines, or does it mean that there were 60 founders and two samples per founder?

120 chromosomes from 60 diploid founders.(5/11/06)

A refSNP report shows 90 individuals were sampled for genotype data. Is 90 the total number of individuals contributing chromosomes for the assay sample size and the population data sample size?

90 is the total number of individuals contributing to individual genotype data. Please note that this number is independent of the assay sample size and the population data sample size since the person(s) who submitted the genotype data may not be the same person who submitted the original assay. In theory, it is possible that the same individuals were used in the discovery assay and for the genotype data, but dbSNP does not always have information with regard to this. (3/9/05)

The “Source” Column

How many times was the variation represented by rs8137714 observed? What population and how many chromosomes did you screen?

Currently, rs8137714 does not have genotype or allele frequency information in dbSNP. To see how the submitted SNPs in this refSNP cluster were mined, do the following:

1.

Go to the refSNP report for rs8137714 and look at the “Submitter Records” section

2.

Click on either of the NCBI Assay ID numbers located on the left. This will take you to the submitted SNP Detail report for the selected SNP.

3.

Scroll down to the Assay section of the Detail Report, and click on the assay “Method” listed there. This will take you to a description of the method used for finding the submitted SNP.

By following the above steps, you can see that both submitted SNPs in this cluster were computationally mined.

If you look at the Validation Summary” section located at the bottom of the refSNP report, you will see that this SNP is a “Double Hit” SNP. In other words, “all alleles have been observed in at least two chromosomes apiece.” You can find more information on Double hit SNPs in the dbSNP FAQ Archive.

Some submitters will submit frequency information for existing refSNP numbers, so it is possible that dbSNP will get frequency information for this refSNP (rs) number in the future. (11/26/07)

How is HWP (Hardy Weinberg Probability) found in the Population Diversity section of the refSNP report determined, and how does it relate to genotype data?

A good explanation of HWP and how it is calculated can be found online. The FAQ Archive also contains information you should find useful. (6/4/07)

Is the heterozygosity score (het score) for rs627099 derived from all four populations? Is there a Han Chinese heterozygosity score available?

Yes, the het score is computed using all available population data. Look in the "Total Samples" (last) row of the Population Diversity section of the refSNP report.

Since the genotype is available for all HapMap samples, the "heterozygosity score" is just the frequency of the "heterozygous genotype". In your example of rs627099, the het score for (Han Chinese) HCB is 0.533, which is the freq for "C/G".(10/31/06)

The refSNP report for rs2839858 doesn’t provide the frequency of each allele and the population diversity section of the report shows that all individuals have the A/A genotype. How can this be a SNP if there are no other observed alleles?

Frequency and genotype data is not required in order to submit SNP assay data, although dbSNP does encourage its submitters to provide frequency and genotype information when submitting a new SNP.

Sometimes SNPs are discovered using a computational algorithm, and in such a case, there are no frequency and genotype data available. Other submitters, however, may submit the frequency/genotype data for such a SNP at a later date. In the case of rs2839858, you can see in the “Population Diversity” section of the report that the exemplar submitted SNP (ss4021194) genotype data was generated by HapMap. It is hard to say if this is truly a "Novariation" site. It might be a rare allele.

I encourage you to contact the submitter directly for more information. You can get the submitter’s contact information by clicking on a submitted SNP number (ss#). For example, if you click on ss48294011, you’ll go to the detail page for that SNP which contains the submitter information. Once on the detail page, click on the submitter’s handle, in this case "SNP500CANCER" to get the contact information.

You can also click on the handle/ submitted SNP ID located in the “Submitter Records” section of the refSNP report to get information on the method of discovery directly from the submitter. For example, if you click on "SNP500Cancer ID|DIO2-05" for ss48294011, you’ll go to the SNP500CANCER page , which contains further details about this particular submitted SNP.(9/14/06)

The refSNP report for rs7503991 shows an A/T variation, but the population diversity section shows the variation was 100% T in all populations. Why is this is listed as a SNP if only 1 allele is observed in all populations?

This refSNP cluster was based on a single submission, which you can look at by clicking on the submitted SNP (ss) number located in the "Submitter records for this refSNP Cluster" section of the refSNP report, which will take you to the . Submitted SNP Detail Report.

The Submitted SNP Detail Report shows that this submission was based on a computer algorithm called SsahaSNP. If you would like to see the publication that describes the SNP discovery method, go to the Assay section of the Submitted SNP Detail Report and click on the method id number to see a description of the method.

The fact that the SNP was shown to be monomorphic in the four populations tested by HapMap could mean a few things. It could mean that there is no variation at this site since the computational method has its limitations. It could also mean that this is a rare SNP that is not present in the four populations tested.(7/3/06)

The refSNP report for rs17362 shows the two genotypes for this refSNP listed simply as "A" and "C". Why do these genotypes look like this rather than the typical "C/C", "A/A", "A/C"?

Since rs17362 maps to the Y chromosome, a genotype of "A" or "C" makes sense. All the genotype data submitted by Oefner has only a single letter. To see Oefner’s submission in submission format, click on the submitted SNP (ss) number on the refSNP page to go to the submitted SNP detail report. Once you are there, go to the “Resource Links” section of the detail report (the located on the top right-hand side of the page), where you’ll find the text “Submission Report” located at the bottom of the section. Click on the blue text “View" located next to the right of the “Submission Report” text.(7/28/06)

I have encountered single letter genotypes for SNPs in XML files that are not located on chromosome Y. rs199930 has a submitted SNP (ss5411833) whose detail report shows genotypes of "C", "T" and "N". How can genotypes like these be possible, and why isn't this data displayed in the refSNP Cluster Report?

Go to the Population Diversity section of the refSNP Cluster Report for rs199930. A member of the cluster, ss5411833, has a genotype from the population "CHMJ". When you click on the blue “CHMJ” text, you’ll see a detailed description of the population sampled. This description indicates that the sampled was a “complete hydatidiform mole” (CHM) which happens to be haploid. dbSNP usually excludes haploid data from genotype frequency computation, but the FTP reports were already generated before the haploid genotype frequency data could be removed. Starting with next build, the FTP files will be corrected.(7/28/06)

Why does dbSNP show each submitted SNP having its own genotype and frequency information? Isn’t this is an over-representation of the number of unique SNPs with these particular attributes?

Although several submitted SNPs are grouped within a single refSNP cluster, each submitted SNP of that cluster can have different sequence data. We capture genotypes on the submitted SNP level to preserve this underlying sequence data, which was used to design the assay for the SNP in question (probes, primers, etc.). When the information is available, Build 126 will have probe identifiers for HapMap genotypes that refer to an Entrez Probe record associated with the individual genotypes. (5/23/06)

In the “Genotype and Frequency Allele Report” for rs7903146, many of the alleles are red, indicating “inconsistent with at least one other submission”. Which do I use?

As you can see in the “Population Diversity” section of rs7903146’s refSNP page, there are many discordant genotypes. I’m sorry to say that we at dbSNP cannot ascertain which is the correct genotype, since dbSNP only collects data and reports a discrepancy in order to alert the user. You must interpret the data yourself. We have no information regarding how or when the error or discrepancy was introduced: it could have been during the chip design, sample preparation and labeling, assay, or during data analysis.

To aid you in your analysis of the discordant data:

Check the submitters' websites to see if you can get any additional genotype information for this variation.

If you do not find helpful information in their websites, contact the submitters directly. By searching dbSNP for the handle, you will find their contact information.

Quite a few dbSNP users are encouraged to contact data submitters directly when they have specific questions about the submitters' data and have received helpful information.(04/07/08)

Could you tell me the minor allele frequency for rs1050622?

This SNP is monomorphic in a CEPH population, according to the frequency data that were submitted for this SNP.

You can see this by looking at the "Population Diversity" section of rs1050622’s cluster report on the rs report. (06/26/08)

Do you have a table that presents the minor allele frequencies for a list of SNPs for the same population found using different genotyping platforms?

This information is available on in the population diversity section of the refSNP cluster report for each SNP.

The refSNP report for rs2037101 shows this variation has a frequency of zero. Does this mean that this polymorphism is not confirmed by population data?

The genotype for rs2037101 was submitted by Hapmap, and it indeed shows no variation frequency. If you click on the submitted SNP number (ss#) in the submitter records section of the refSNP report, you can see the details for ss2946401 (the original SNP for this refSNP). As you can see from this report, the original SNP was submitted by TCS. If you click on the link next to the word “Method” in the assay section of the submitted SNP (ss) report, you’ll get a description of the method used to detect this SNP. In this case, the method used to discover the SNP was computational, and as such, it must be validated by genotypes, or by frequency, or by separate independent observations. As of this writing, that has yet to occur. (11/03/06)

The refSNP report for rs2839858 doesn’t provide the frequency of each allele and the population diversity section of the report shows that all individuals have the A/A genotype. How can this be a SNP if there are no other observed alleles?

Frequency and genotype data is not required in order to submit SNP assay data, although dbSNP does encourage its submitters to provide frequency and genotype information when submitting a new SNP.

Sometimes SNPs are discovered using a computational algorithm, and in such a case, there are no frequency and genotype data available. Other submitters, however, may submit the frequency/genotype data for such a SNP at a later date. In the case of rs2839858, you can see in the “Population Diversity” section of the report that the exemplar submitted SNP (ss4021194) genotype data was generated by HapMap. It is hard to say if this is truly a "Novariation" site. It might be a rare allele.

I encourage you to contact the submitter directly for more information. You can get the submitter’s contact information by clicking on a submitted SNP number (ss#). For example, if you click on ss48294011, you’ll go to the detail page for that SNP which contains the submitter information. Once on the detail page, click on the submitter’s handle, in this case "SNP500CANCER" to get the contact information.

You can also click on the handle/ submitted SNP ID located in the “Submitter Records” section of the refSNP report to get information on the method of discovery directly from the submitter. For example, if you click on "SNP500Cancer ID|DIO2-05" for ss48294011, you’ll go to the SNP500CANCER page , which contains further details about this particular submitted SNP.(9/14/06)

The population diversity section of the rs11545130 cluster report shows an A-to-G change, but the integrated maps section shows a C nucleotide.

You are correct that the cluster report shows the variation in two different orientations. The integrated maps section of the cluster report shows the variation in the reference sequence (NT_011520.11) orientation, while the population diversity section reports the frequency and allele data in refSNP orientation (the orientation of the cluster exemplar), which is why it was reported as A/G.

There are a number of reasons that we need to report RefSNP data based on RefSNP orientation defined by rs FASTA rather than based on reference sequence orientation:

• Sometimes a SNP maps to multiple reference sequences each of which have different orientations.
• Sometimes a SNP doesn't map to any genome position.
• Sometimes the NCBI reference sequence and the Celera or HuRef contigs are of different orientations.
• Between genome builds, contig sequences may change between different versions (although these changes becoming more rare as the contigs mature).

(08/01/08)

How many times was the variation represented by rs8137714 observed? What population and how many chromosomes did you screen?

Currently, rs8137714 does not have genotype or allele frequency information in dbSNP. To see how the submitted SNPs in this refSNP cluster were mined, do the following:

1.

Go to the refSNP report for rs8137714 and look at the “Submitter Records” section

2.

Click on either of the NCBI Assay ID numbers located on the left. This will take you to the submitted SNP Detail report for the selected SNP.

3.

Scroll down to the Assay section of the Detail Report, and click on the assay “Method” listed there. This will take you to a description of the method used for finding the submitted SNP.

By following the above steps, you can see that both submitted SNPs in this cluster were computationally mined.

If you look at the Validation Summary” section located at the bottom of the refSNP report, you will see that this SNP is a “Double Hit” SNP. In other words, “all alleles have been observed in at least two chromosomes apiece.” You can find more information on Double hit SNPs in the dbSNP FAQ Archive.

Some submitters will submit frequency information for existing refSNP numbers, so it is possible that dbSNP will get frequency information for this refSNP (rs) number in the future. (11/26/07)

Two reports for rs3676330 claim that the variation for mouse strains C57BL/6J and 129S1/SVIMJ are T and A, respectively, whilst the third report claims the reverse. Which report is correct and why are the letters highlighted in green?

The two submissions were on opposite strands, so they actually both agree and that is why they are colored green.

Expand the SNP detail section (by click on the blue plus sign) at the bottom of the page for strand orientation details. (10/04/05)

How do I find the set of alleles that you used to instantiate a SNP allele sequence?

We do not choose the alleles for a SNP. We include all alleles reported by submitters for a refSNP cluster. If a submitted SNP is on the reverse strand relative to the refSNP sequence, we reverse the alleles. For example, in the refSNP(rs) cluster rs268, rs268and ss268 have the allele A/G, while ss48420135 shows the C/T allele on the reverse strand. So the reported allele set for refSNP cluster rs268 is reported as A/G.

(6/21/06)

Why do web queries of rs939820, rs10205833, and rs7597158 return sequences that do not match the exemplar sequences for these SNPs found using a database query?

When you refer to the sequences as ”not matching”, I assume that you are referring the fact that they don’t match at the point of variation, since in rs939820, for example, the two flanking sequences are the same with the exception of the point of variation.

On the RefSNP (rs) page, we show the rs FASTA using the IUPAC code for variations, while on the submitted SNP (ss) page, we show the ss fasta using the submitted observed sequence. In most cases, all member ss of an rs cluster have the same allelic states in the same orientation, so the rs variation matches the ss exemplar variation. There are cases, however, where the rs variation does not match the ss exemplar variation. For example, if an ss exemplar has an A/G variation, and another ss from the cluster in the same orientation has an A/T variation, then the rs allele list will read A/G/T since it includes all member ss alleles. If you viewed the rs allele list converted into IUPAC code (remember the refSNP page shows the flanking sequence in IUPAC), it would show a D representing A or G or T.

Most of the submitted SNPs have the same variations in the rs clusters you mentioned, but one or two of the ss in each cluster have an extra allele. All of the ss in the rs939820 cluster have an A/G variation, with the exception of one ss that has an -/A/G variation. All the ss in the rs10205833 cluster have a C/G variation, with the exception of one ss that has a C/G/T variation. Most of the ss in the rs7597158 cluster have an A/G variation, while the ss exemplar has a -/G variation. In these cases, the refSNP page variation list includes all allelic states: for rs939820, instead of an R, it is N; For rs10205833, instead of an S, it is B that represents for C or G or T; for rs7597158, since the ss exemplar has a -/G variation, while most of the other ss in this cluster have an A/G variation, the refSNP FASTA shows an N at the variation point.

I will update dbSNP’s variation representation for "mixed variation" clusters to include all the allele lists from all the submitted SNPs.(8/18/06)

rs135551 is marked reverse (“rev”) in dbSNP, but is actually in forward orientation in the genome (chromosome 22). This orientation discrepancy is proving difficult.

rs135551 is a refSNP Cluster with 12 submitted SNP(ss) numbers. An ss number gets assigned to a refSNP (rs) cluster based on flanking alignment similarity. An ss number can be either in forward or reverse orientation with respect to its rs cluster. The "rev" in the submission section of the refSNP report shows the strand orientation of the member ss numbers in the cluster with respect to the refSNP.

If you look in the FASTA section of the report, you will see the flanking sequence for rs135551, with the sequence closest to the variation reading as follows:

TTAGACTCAG Y GAGGACAGTC

The above flanking sequence aligns to chromosome 22 in the reverse orientation on both the NCBI and the Celera assemblies.

I’m guessing that in your alignment to chromosome 22, you used an ss number within the cluster that had reverse orientation with respect to rs135551, and hence got your forward orientation result. (10/17/07)

How is “orientation” determined in the “Submitter Records” section of the refSNP report? Is it the submitted SNP orientation with respect to the plus and minus strands?

The orientation is the orientation of the submitted SNP with respect to the refSNP (either plus or minus strand of the refSNP). Sequences are always shown as 5'->3'.(10/31/07)

Will refSNP flanks change orientation between builds?

A refSNP’s flanking sequence will never change orientation, but a refSNP’s orientation with respect to the genome may change between builds if the genome assembly itself has significant changes that occur between builds. This was the case in the earlier human genome builds, but the human genome build is more stable now, so orientation changes such as this will occur less often.

There are several different orientation types which exist in dbSNP:

• The orientation of a submitted SNP(ss) flank with respect to the RefSNP cluster (rs) flank.
• The orientation of the rs flank with respect to the contig sequence.
• The orientation of the contig sequence with respect to the genome.
  Please note that all placed human contigs are in the same orientation as genome.
• The orientation of a refSNP with respect to the genome.
  Since all placed contigs have the same orientation as genome, this orientation is the same as rs orientation to contig in human.
• The orientation of an mRNA with respect to the contig.
  This might not be related to our discussion here, but I mention it since it might come up in another context.

We make sure that a refSNP’s flanking sequence orientation never changes: If a new ss is added to a refSNP cluster, and if that new ss has the longest flanking sequence (and therefore becomes the exemplar of the cluster), but has reverse orientation with respect to the existing rs, we reverse its flanking sequence when it becomes the new rs flank. (11/20/07)

I am interested in retrieving flanking sequences in the forward orientation for a list of b126 SNPs. How do I do this?

A refSNP (rs) flanking sequence is simply the flanking sequence of the longest submitted SNP (ss) in the refSNP cluster. The ss with the longest flanking sequence is called the "refSNP exemplar". If a refSNP cluster gets a new ss member added after build 126 and this new ss has flanking sequence that is longer than the flanking sequences of the existing ss in the cluster, then the new ss becomes the refSNP cluster’s exemplar, its flanking sequence is adjusted for orientation, and it will be used as the rs cluster’s flanking sequence in the next build. Since the new ss will, in most cases, align at the same position as the rs, the flanking sequence difference should be small. I am therefore curious why you want would need the rs flanking sequence for build 126. Have you noticed a significant difference (other than length) between rs flanks in different builds?

In general, dbSNP does not keep old build data due to data size issues and the complexity of tracking assembly changes between builds. However, if you have a local copy of dbSNP, you can access the rs flanking sequence for a particular build since dbSNP keeps the flanking sequences of all submitted SNPs. If you do not have a local copy of dbSNP that you can query, give us a list of the rs numbers in question, we can pull the data for you.(11/20/07)

Define the term “orientation” as used in dbSNP.

Submissions to our database have arbitrary orientation relative to each other. If multiple submissions refer to the same SNP, they may cluster together in reverse orientation, so we also track the orientation of each submission relative to the exemplar ss. Please bear in mind that submitters to dbSNP are only required to provide some flanking sequence around the SNP for context. The SNPdev team does the positioning using BLAST and the resulting alignments. (3/13/05)

How do I determine the orientation of dbSNP’s allele frequency data?

On the refSNP page, allele frequency is always reported in the same orientation as the flanking sequence in the refSNP page FASTA section. When frequency data is submitted, we ask the submitter to specify strand information using tags like: SS_STRAND_FWD, SS_STRAND_REV, RS_STRAND_FWD and RS_STRAND_REV. If no strand tags are submitted, we assume the strand is in the same orientation as the submitted SNP or the refSNP. When computing refSNP allele frequency, we reverse the alleles when necessary. Sometimes frequency data is submitted for the wrong strand. If the alleles are A/T or C/G, we have no way of knowing that they have been submitted improperly. Please contact vog.hin.mln.ibcn@nimda-pns if you find any errors in frequency data.

I have found a refSNP in dbSNP with its flanking sequence in reverse orientation (anti-sense orientation) for the LIG1 gene. Kindly update your database.

rs11879148 is in reverse orientation with respect to mRNA NM_000234 for the LIGI gene because the flanking sequence of a submitted SNP for that cluster was used as the refSNP (rs) cluster flanking sequence, so the orientation of the flanking sequence for a refSNP cluster doesn't depend on the orientation of a contig sequence or mRNA sequence.

The mRNA orientation column in the "GeneView" section of the refSNP page for rs11879148 shows that this SNP is in reverse orientation with respect to the mRNA for LIG1. To insure that a refSNP’s orientation is stable throughout various builds, we do not change the refSNP flanking sequence. We also apply this rule to those SNPs that map to multiple positions or do not map to genome at all.(6/29/06)

I think "alleles" and "db SNP allele" may be switched in rs28944222, where dbSNP shows A/G; S, P; and in rs28944221 where dbSNP shows T/C; N, and D.

Both of these rs numbers mapped to the reverse strand of the contig, while the mRNA mapped to the forward strand:

========================> Contig [Forward]

-------------> mRNA [Forward]

<------ SNP [Reverse]

You must therefore use the complementing nucleotides of the SNP alleles in order to get the correct codon, which will in turn, code for the correct amino acid:

T/C is the complement of A/G and codes for S, P

A/G is the complement of T/C and codes for N, D (1/5/06)

rs4897909 and rs4788229 are 4 base pairs apart, but if I superimpose the flanking sequences of both, the “K” variation of rs4897909 corresponds to an “A” base on the flanks of rs4788229.

The fact that rs4897909's G/T(K) aligns with rs4788229 base "A" in the same orientation does seem curious. These two rs numbers are both from the same computational SNP discovery program (SSAHA — you will find references to this program by reviewing the publications associated with these SNPs), and there are no other submitted SNP clusters that map to the same position. Also, there is no population frequency or individual genotype validation information available for these two SNPs.

Based on above information, I’m guessing that the "K" erroneously aligns to "A" in the same orientation for the following reasons:

First, the NCBI build has progressed to 36, whereas these SNPs were discovered on build 31. It might be that the build 31 contig upon which the SNP comparison was based contains errors. An example supporting this supposition: rs4897909 was based on a single submitted SNP (ss) from SSAHA: WI_SSAHASNP|NT_025920.10_372470, but searching NCBI for NT_025920 shows that this contig has been removed from the current genome build.

Second, dbSNP sets the SNP validation status based on frequency/genotype information or multiple submissions from non-computational methods. Roughly half of the SNPs in dbSNP are validated. At the present time, these two SNPs are not validated, and therefore can be considered suspect. (9/5/06)

Are the M, Y, R, W, K and S codes you use in the FASTA sequence at the SNP position designed by American Association of Biochemistry?

Yes. We use IUPAC codes in FASTA sequences at the SNP position. You can find the IUPAC code in many websites. Here is an example of one such listing.(07/22/08)

In SNP flank sequence, I find that some bases are capital letters, while others are in lowercase (small) lettering. What is the difference between the two?

Sequence in lowercase (small letters) has been identified by RepeatMasker as low-complexity or repetitive elements. You can find this description by clicking on the "Legend" link located above the sequence, which will take you to a sequence descriptions page. (9/23/05)

What does N/N represent in refSNP sequence?

N/N is the IUPAC code used to indicate that the actual base can't be determined by a genotyping assay. (11/17/05)

I have come across nucleotide representations that I don’t understand. What does “R” mean?

"R" is part of the IUPAC code for nucleotide variations which represents "A" or "G". You can find all of the IUPAC nucleotide codes online. (3/9/05)

How do I determine the distance up and downstream that the sequence for rs3208856 extends?

The sequence submitted for this rs number is located in the FASTA section of the refSNP cluster report for rs3208856. The FASTA data show that rs3208856 has 50 bp on each side of the variation. Go to the Integrated Maps section of the RefSNP report, and click on the rs number link located in the NCBI Sequence Viewer field to see more sequence surrounding this SNP.

On the refSNP page, where do I find information about amino acid changes resulting from the variation?

When a SNP causes an amino acid change, you can see the changes in the Gene View section of the refSNP report (example). The Gene View section is located about half way down the refSNP report page. (1/13/06)

Where is the resource that allows you to actually see in a graphic how many SNPs are known to lie within a particular gene, and their physical coordinates?

The resource you refer to is the sequence viewer graphical display of a gene region on the human genome. We had to discontinue this resource because the NCBI sequence viewer itself fails when the sequence under consideration is very large (contig sized).

You can still get a sequence view of the mRNA record using the seqview button on the Entrez SNP display, but this won't show intronic SNPs. There may be other inconsistencies even among coding SNPs since the position of SNPs on mRNAs is taken from a different mapping pipeline then the one used to compute genomic locations.

For now, you can search Entrez SNP using the gene symbol or gene id and click the 'GeneView' icon on any of the displayed rs records:

1.

Go to Entrez SNP and enter the search terms “LPL AND Human” (without the quotation marks) into the text box at the top of the page, and click on The “Go” button.

2.

You will get a page back that contains 158 results to your query.

You can also use Entrez SNP to get a rough text representation of a SNP position in a gene by entering the gene symbol in the search box at the top of the page. When you get the result page, select “chromosome report” from the “display” drop-down menu and “Chromosome Base Position” from the “sort by” drop-down menu. (6/3/05)

Are there any refSNP fields that indicate which SNP allele matches the reference genome sequence upon which the SNP was mapped?

We maintain the contig variant in one of our database tables, called SNPContigLoc, which is located in the organism_data directory of your organism’s database. Once you locate the organism_data directory (the previous link is to the human_9606 directory as an example), download SNPContigLoc.bcp.gz. The first column of this table is snp_id. The last column of this table contains the contig form of the variation (in SNP orientation rather than in contig orientation). When the orientation in the next to the last column of this table is set to one, you'll have to reverse complement if you want the contig orientation.

Where do I find contact information for the submitter of rs12638783, as well as more detailed information about this refSNP?

You can get reports for a particular SNP by going to the dbSNP home page and entering “rs12638783” in the text box located in the “Search by IDs” section of the page, and then pressing the “search” button.

There is a Reference SNP (rs) report as well as a submitted SNP (ss) detail report and a ss detail report in submission format available for rs12638783. To get contact information for the submitter, click on the submitter handle in either of the ss reports. Please note that no frequency data was submitted for this SNP. (4/13/05)

How do I determine who submitted rs11544612?

Go to the rs11544612 refSNP page and scroll down to the “Submitter Records for this refSNP Cluster” section. Click on the text that reads: “ss16240609” (the only submitted SNP for this cluster) to go to the “Submitted SNP Detail” page for this ss number. Once you are on the detail page, click on the text for the submitter handle, which in this case is “CGAP-GAI”, to go to the “SNP Submitter Contact Detail” page, which contains all full name of the submitting individual or institution along with their contact information.(9/7/06)

How can I find the references for ss42780946 & ss460400? I’ve looked in what I thought to be obvious places, but can’t find them in dbSNP.

Here is how you find the references:

1.

Go to the dbSNP home page, and enter ss42780946 in the text box located in the "Search by ID on all Assemblies" section located just below the announcement section near the top of the page, and select "NCBI Assay ID(ss#)" from the drop down menu to the right of the text box where you entered ss42780946. Click the "search" button.

2.

The resulting submitted SNP report will appear. Scroll down this report until you get to the "Individual Genotype Batch" section where you'll see "View citation details". Click on the numeral "1" link just to the right of these words.

3.

The resulting publication detail page does not indicate the actual reference, but if you click on the number that follows the word "PMID" near the top of the page, you will get to the actual publication reference.

I'm sorry the link to the reference is not clear, but I will mention it to the SNP development team, and perhaps they can work out something that will make it easier to see. (8/8/07)

Is "Ter" an abbreviation for a termination codon?

Yes. "Ter" is an abbreviation for a termination codon. (9/30/05)

What does TER[*] for a non-synonymous coding change mean?

TER[*] means that the variation changed the codon to a termination codon (Ter or *), which causes premature termination of the protein. (10/25/06)

What does cSNP mean?

A cSNP is a SNP located in the coding region (exon) of a gene.

Some synonymous SNPs in dbSNP are annotated on mRNA as "complement", and are not shown on the protein. What does "complement" mean, and why is annotation different for dbSNP and RefSeq?

"Complement" means that the SNP mapped to the complementary strand of the mRNA. The SNP will map to the compliment if the mRNA is in the reverse orientation with respect to the genome and the SNP is maps in the forward orientation.

Example:

variation complement(1601)

/gene="IFIH1"

/gene_synonym="Hlcd; IDDM19; MDA-5; MDA5; MGC133047"

/replace="a"

/replace="g"

/db_xref="dbSNP:10930046"

In the above example, the mRNA is on the reverse orientation with respect to the genome, and the SNP (i.e. rs10930046 [C/T])is on the forward orientation. You can see this in the GeneView section of the refSNP cluster page for this SNP. Synonymous SNPs that do not change the amino acid are not reported on the protein.(06/19/09)

What does “contig reference mean?

“Contig reference” refers to an allele on a contig at a particular SNP position. For example, if a synonymous or non-synonymous SNP at a particular contig location has the variation of “C/T” and the “contig reference for that SNP is “T”, then the SNP would be “T” at that SNP location on the contig.

How does dbSNP define a double-hit SNP?

A double-hit SNP is a SNP where all alleles have been observed in at least two chromosomes apiece.

What is the definition of the population described in a SNP report?

A "population" is submitted and defined by a submitter, which means that the submitter provides a population ID (an abbreviation) as well as a description of the population, therefore, “populations” are not curated by dbSNP.

Please note that genotype data also have populations, but the "population with frequency data" designation is only for populations that have allele frequency submissions, and these do not include genotype submissions.

You can see how major contributors to dbSNP define their populations by going to the “Search/View Population Detail” page and type in the submitter handles "Perelgen" and "CSHL-HapMap" in the search text box located in the grey search section and clicking the “Search” box directly below. (3/9/05)

What does it mean when an SNP is labeled “synonymous” or “non-synonymous”?

The terms “synonymous” and “non-synonymous” are used for SNPs that are in predicted protein coding regions (i.e., exons of genes). Synonymous SNPs are those SNPs that have different alleles that encode for the same amino acid. Non-synonymous SNPs are SNPs that have different alleles that encode different amino acids. For further details, I recommend querying for “genetic code” or “protein translation” at the NCBI books website.

What is the difference between assay sample size and population data sample size?

The assay size is the number of chromosomes examined to ascertain or detect the SNP, while the population sample size is the number used in determining the frequency of the SNP. Sometimes the sample size will be the same in both cases if the same group detected and determined a SNP frequency using the same population. (9/1/05)