ClinVar Genomic variation as it relates to human health
NM_000140.5(FECH):c.315-48T>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic(11); Likely pathogenic(2); Pathogenic, low penetrance(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000140.5(FECH):c.315-48T>C
Variation ID: 562 Accession: VCV000000562.41
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 18q21.31 18: 57571588 (GRCh38) [ NCBI UCSC ] 18: 55238820 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 May 12, 2024 Mar 25, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000140.5:c.315-48T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
intron variant NM_000140.4:c.315-48T>C NM_001012515.4:c.333-48T>C intron variant NM_001371094.1:c.315-48T>C intron variant NM_001371095.1:c.99-48T>C intron variant NM_001374778.1:c.315-48T>C intron variant NC_000018.10:g.57571588A>G NC_000018.9:g.55238820A>G NG_008175.1:g.20150T>C LRG_1080:g.20150T>C LRG_1080t1:c.315-48T>C LRG_1080t2:c.333-48T>C - Protein change
- Other names
- IVS3AS, T-C, -48
- Canonical SPDI
- NC_000018.10:57571587:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
0.13738 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.03737
The Genome Aggregation Database (gnomAD) 0.06200
Trans-Omics for Precision Medicine (TOPMed) 0.07570
Exome Aggregation Consortium (ExAC) 0.10730
The Genome Aggregation Database (gnomAD), exomes 0.11807
1000 Genomes Project 30x 0.13398
1000 Genomes Project 0.13738
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
FECH | - | - |
GRCh38 GRCh37 |
306 | 403 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (14) |
criteria provided, conflicting classifications
|
Mar 25, 2024 | RCV000000592.24 | |
no classifications from unflagged records (1) |
no classifications from unflagged records
|
Feb 15, 2024 | RCV000414979.5 | |
Pathogenic/Pathogenic, low penetrance (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV001381522.22 | |
Pathogenic (1) |
criteria provided, single submitter
|
Oct 4, 2023 | RCV001195427.7 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(Dec 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: yes
Allele origin:
germline
|
Institute of Human Genetics, University Hospital Muenster
Accession: SCV002496157.1
First in ClinVar: Apr 08, 2022 Last updated: Apr 08, 2022 |
Comment:
ACMG categories: PM3,PP6,BS2
Number of individuals with the variant: 1
Clinical Features:
Increased erythrocyte protoporphyrin concentration (present)
Age: 10-19 years
Sex: female
Tissue: blood
|
|
Pathogenic
(May 12, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002579902.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PM3_VSTR, PS4, PP1_STR, PS3_SUP
|
Number of individuals with the variant: 1
Sex: male
|
|
Pathogenic
(May 26, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002767242.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. However, individuals with a single heterozygous FECH variant are reported to also manifest the phenotype (PMID: 20105171). 0112 - Heterozygous variants in this gene have been reported to have reduced penetrance (OMIM). (N) 0210 - Splice site variant (non-canonical) proven to affect splicing of the transcript with a known effect on protein structure (intron 3 of 10). This variant was shown to cause aberrant splice and is predicted to result in nonsense-mediated decay (NMD) (PMID: 16385445; PMID: 16958804). (P) 0251 - Variant is heterozygous. (N) 0307 - Variant is present in gnomAD >=0.05 (23726 heterozygotes, 3957 homozygotes). (B) 0506 – Splicing in silicos tools are inconclusive, nucleotide is poorly conserved. (N) 0701 - Comparable NMD predicted variants have very strong previous evidence for pathogenicity (PMID: 20105171). (P) 0801 – Strong previous evidence of pathogenicity in unrelated individuals. This variant has been previously reported as a hypomorphic allele that causes erythropoietic protoporphyria when in trans with a deleterious variant (ClinVar, PMID: 16385445; PMID: 31304091). (P) 1001 - Strong functional evidence supporting abnormal protein function. Studies with both homozygous and heterozygous patients show significantly reduced FECH activity compared to wild-type (PMID: 16385445; PMID: 16958804). (P) 1101 - Very strong and specific phenotype match. (P) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
|
|
Pathogenic
(Dec 13, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV003853551.1
First in ClinVar: Apr 09, 2023 Last updated: Apr 09, 2023 |
|
|
Pathogenic
(Jun 01, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004020467.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
Variant summary: FECH c.315-48T>C is located at a position not widely known to affect splicing. Four/four computational tools predict the variant has no significant impact … (more)
Variant summary: FECH c.315-48T>C is located at a position not widely known to affect splicing. Four/four computational tools predict the variant has no significant impact on splicing, while one predicts that the variant strengthens a cryptic 3' acceptor site, located 63 nucleotides upstream from the canonical site. One publication reports experimental evidence confirming that this variant affects mRNA splicing, i.e. strengthening the activity of a cryptic splice site (a constitutive aberrant acceptor splice site), located 63 nucleotides upstream from the canonical site, thus increasing the amount of the aberrant transcripts from ~20% (normal) to ~40% (Gouya_2002). The variant allele was found at a frequency of 0.11 in 281694 control chromosomes, including 3957 homozygotes (gnomAD). In addition, this variant is reported with even higher allele frequencies in certain subpopulations, i.e. in the Latino- and East Asian subpopulations, with a frequency of frequency of 0.34 and 0.33, respectively. The observed variant frequency and the high number of homozygotes suggests that the variant is benign, even when found in homozygous state. However, this variant (c.315-48T>C) has been reported in the literature in over 95% of patients affected with Erythropoietic Protoporphyria (EPP), who were all compound heterozygotes for a pathogenic LoF variant in trans (e.g. Gouya_2002, Colombo_2013, Yasuda_2019). In addition, a mild disease phenotype with incomplete penetrance was also reported for homozygotes (e.g. Mizawa_2016). These data suggest that the pathogenicity (severity and penetrance) of the variant is genotype-dependent, i.e. largely determined by the variant observed in trans. Publications reporting experimental evidence suggest that the abnormally spliced mRNA is degraded by NMD (Gouya_2002), and FECH activity in peripheral blood lymphocytes from individuals who were homozygous for the C-allele was ~38% compared to individuals who were homozygous for the T-allele (Tahara_2010). The following publications have been ascertained in the context of this evaluation (PMID: 22591014, 16385445, 11753383, 26280465, 21132468, 30594473). Thirteen ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance, two as likely pathogenic, and nine as pathogenic. Based on the evidence outlined above, the variant seems to be a hypomorphic allele that is subject to interallelic interactions which might result in an incomplete penetrance, however it is considered pathogenic, when in found in trans with a LoF variant. (less)
|
|
Pathogenic
(May 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004041112.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
|
|
Pathogenic
(Sep 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV004235806.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
Pathogenic, low penetrance
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001579958.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change falls in intron 3 of the FECH gene. It does not directly change the encoded amino acid sequence of the FECH protein. … (more)
This sequence change falls in intron 3 of the FECH gene. It does not directly change the encoded amino acid sequence of the FECH protein. This variant is present in population databases (rs2272783, gnomAD 35%), including at least one homozygous and/or hemizygous individual. This mild variant has been observed in combination with another severe FECH variant in over 90% of individuals with congenital erythropoietic porphyria (PMID: 16385445, 23364466). The vast majority of individuals that are homozygous for this variant do not have clinical symptoms, even in the presence of mild biochemical abnormalities (PMID: 11753383, 29941360). However, a few individuals with milder symptoms have been reported (PMID: 1729699, 16958804, 18758989, 26280465). ClinVar contains an entry for this variant (Variation ID: 562). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, this variant is reported to cause disease. However, as this variant is associated with a lower penetrance than other pathogenic alleles in the FECH gene, it has been classified as Pathogenic (low penetrance). (less)
|
|
Pathogenic
(Oct 04, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal erythropoietic protoporphyria
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV001365780.2
First in ClinVar: Jul 04, 2020 Last updated: Apr 20, 2024 |
Comment:
The c.333-48T>C variant in FECH is a well-established pathogenic variant for erythropoietic protoporphyria (EPP; Gouya 2002 PMID: 11753383, Gouya 2006 PMID: 16385445, ClinVar Variation ID … (more)
The c.333-48T>C variant in FECH is a well-established pathogenic variant for erythropoietic protoporphyria (EPP; Gouya 2002 PMID: 11753383, Gouya 2006 PMID: 16385445, ClinVar Variation ID 562). This variant is found in >95% of individuals with FECH-associated EPP but has also been identified in 6.7% (10341/152102) of pan-ethnic chromosomes in gnomAD, including 817 homozygous individuals (http://gnomad.broadinstitute.org, v3.1.2). In vitro and in vivo functional studies demonstrate that the variant leads to aberrant splicing resulting in a mild but significant reduction in enzyme activity levels (Gouya 2002 PMID: 11753383, Barman-Aksözen 2017 PMID: 28093505). The majority of individuals with FECH-associated EPP carry this hypomorphic c.333-48T>C variant in compound heterozygosity with a rare loss-of-function allele, resulting in enzyme activity levels that are reduced by >70%. Most individuals who are homozygous for the c.333-48T>C variant do not exhibit any clinical symptoms despite having mild biochemical abnormalities; however, a few individuals with milder symptoms such as erythema on the face and extremities, mild photosensitivity after sun exposure have been reported (Mizawa 2016 PMID: 26280465, Alagappan 2017 PMID: 28054335), suggesting that the penetrance and disease severity associated with this variant is determined by the type of variant observed on the second copy of the FECH gene (in trans). In summary, despite its frequency in the general population, this variant is a hypomorphic allele that meets criteria to be classified as pathogenic for autosomal recessive EPP and is expected to cause more severe disease when in compound heterozygosity with a loss-of-function allele. ACMG/AMP Criteria applied: PM3_VeryStrong, PP1_Strong, PS3_Moderate. (less)
|
|
Pathogenic
(Jan 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV002563477.11
First in ClinVar: Aug 23, 2022 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
|
|
Pathogenic
(Aug 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: yes
Allele origin:
germline
|
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota
Accession: SCV000889972.1
First in ClinVar: Jun 22, 2018 Last updated: Jun 22, 2018 |
Number of individuals with the variant: 1
|
|
Likely pathogenic
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001140907.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
Pathogenic
(Jan 22, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002556470.2
First in ClinVar: Aug 04, 2022 Last updated: Dec 17, 2022 |
Comment:
In summary, despite its frequency in the general population, this variant meets criteria to be classified as pathogenic for autosomal recessive EPP; however, it should … (more)
In summary, despite its frequency in the general population, this variant meets criteria to be classified as pathogenic for autosomal recessive EPP; however, it should be noted that this variant is only expected to cause disease when in compound heterozygosity with a loss-of-function allele. (less)
|
|
Pathogenic
(Oct 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001950493.4
First in ClinVar: Oct 02, 2021 Last updated: Nov 25, 2023 |
Comment:
Observed in the apparent homozygous state in multiple individuals with an erythropoietic protoporphyria phenotype that was reported as either mild or typical and slightly increased … (more)
Observed in the apparent homozygous state in multiple individuals with an erythropoietic protoporphyria phenotype that was reported as either mild or typical and slightly increased erythrocyte-free protoporphyrin concentration or decreased FECH expression (Mizawa et al., 2016; Brancaleoni et al., 2018), but also observed in the apparent homozygous state in a few unaffected individuals from these two studies as well as in numerous individuals in large population cohorts (gnomAD); Published functional studies demonstrate abberant splicing and a mild reduction in enzyme activity (Gouya et al., 2002; Barmin-Aksozen et al., 2017); In silico analysis supports that this variant does not alter splicing; This variant is associated with the following publications: (PMID: 34758253, 21132468, 22591014, 29854403, 30712775, 32313951, 28054335, 28026050, 28093505, 31304091, 23364466, 12601550, 16385445, 18758989, 26280465, 16958804, 29941360, 11753383) (less)
|
|
Uncertain significance
(Mar 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806115.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
|
|
Pathogenic
(Sep 01, 2007)
|
no assertion criteria provided
Method: literature only
|
PROTOPORPHYRIA, ERYTHROPOIETIC, 1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000020741.3
First in ClinVar: Apr 04, 2013 Last updated: Jun 22, 2018 |
Comment on evidence:
Erythropoietic protoporphyria-1 (EPP1; 177000) most often results from inheritance of this low-expression mutation (IVS3-48C) in trans with a null FECH allele (Herrero et al., 2007). … (more)
Erythropoietic protoporphyria-1 (EPP1; 177000) most often results from inheritance of this low-expression mutation (IVS3-48C) in trans with a null FECH allele (Herrero et al., 2007). Gouya et al. (2002) described an intronic single-nucleotide polymorphism, IVS3-48T-C, that modulates the use of a constitutive aberrant acceptor splice site. The aberrantly spliced mRNA is degraded by a nonsense-mediated decay mechanism, producing a decreased steady-state level of mRNA and the additional FECH enzyme deficiency necessary for EPP phenotypic expression. Gouya et al. (2002) suggested that this explained the incomplete penetrance of EPP. Using 25 families with EPP caused by identified mutations, they unambiguously determined the haplotypes of 19 independent chromosomes bearing a normal-expression allele and 23 independent chromosomes bearing a low-expression allele in trans to the mutated allele in asymptomatic carrier parents and individuals with overt EPP, respectively. By genotyping of 25 family members with EPP, they showed that, in trans to a specific FECH mutated allele, only the IVS3-48C polymorphism cosegregated with low-expression FECH allele in all individuals with overt EPP. Moreover, the IVS3-48T polymorphism cosegregated with the normal-expression allele in all the asymptomatic carriers. Genotyping of 40 additional unrelated individuals with EPP revealed that 38 had an IVS3-48C allele. Analysis of the intron 3/exon 4 sequence revealed the presence of a cryptic acceptor splice site 63 bp upstream from the one that is normally used. To test the effect of the IVS3-48T-C transition on splicing efficiency, Gouya et al. (2002) subcloned in a eukaryotic expression vector a 1,936-bp genomic fragment spanning exons 3-4 that differed only at the T/C nucleotide. Transfection of the IVS3-48C and IVS3-48T minigenes showed that in both cases the physiologic and the predicted cryptic acceptor sites were used, but with different efficiency. The IVS3-48C minigene gave rise to 40% aberrantly spliced mRNA, and the IVS3-48T minigene to only 20%. To confirm in a larger cohort that the low expression of a wildtype allelic variant is generally required for EPP to be clinically expressed, Gouya et al. (2004) studied 55 patients and a control group of 80 unrelated subjects of Caucasian origin. They confirmed that the wildtype low-expressed allele phenomenon is usually operative in a mechanism suggesting incomplete penetrance in EPP. Gouya et al. (2006) showed that the frequency of the IVS3-48C allele differed from 43% in Japanese to less than 1% in black West Africans. They concluded that the mutation may have occurred not long after the Diaspora out of Africa. (less)
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Protoporphyria, erythropoietic, 1
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760431.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
|
|
not provided
(-)
|
no classification provided
Method: literature only
|
Protoporphyria, erythropoietic, 1
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000054467.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
|
|
Uncertain significance
(Jan 25, 2016)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
Erythema
Jaundice
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492647.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
|
|
Uncertain significance
(Jan 01, 2016)
|
Flagged submission
flagged submission
Method: clinical testing
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
Protoporphyria, erythropoietic, 1
Affected status: yes
Allele origin:
unknown
|
Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368184.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Uncertain significance.
|
|
click to load more click to collapse | |||||
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Characterization of a novel pathogenic variant in the FECH gene associated with erythropoietic protoporphyria. | Kieke MC | Molecular genetics and metabolism reports | 2019 | PMID: 31304091 |
Recent advances on porphyria genetics: Inheritance, penetrance & molecular heterogeneity, including new modifying/causative genes. | Yasuda M | Molecular genetics and metabolism | 2019 | PMID: 30594473 |
Digital PCR (dPCR) analysis reveals that the homozygous c.315-48T>C variant in the FECH gene might cause erythropoietic protoporphyria (EPP). | Brancaleoni V | Molecular genetics and metabolism | 2018 | PMID: 29941360 |
Modeling the ferrochelatase c.315-48C modifier mutation for erythropoietic protoporphyria (EPP) in mice. | Barman-Aksözen J | Disease models & mechanisms | 2017 | PMID: 28093505 |
Ferrochelatase gene mutation in Singapore and a novel frame-shift mutation in an Asian boy with erythropoietic protoporphyria. | Alagappan U | International journal of dermatology | 2017 | PMID: 28054335 |
Erythropoietic Protoporphyria, Autosomal Recessive. | Adam MP | - | 2017 | PMID: 23016163 |
Incomplete erythropoietic protoporphyria caused by a splice site modulator homozygous IVS3-48C polymorphism in the ferrochelatase gene. | Mizawa M | The British journal of dermatology | 2016 | PMID: 26280465 |
Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-linked protoporphyria. | Balwani M | Molecular medicine (Cambridge, Mass.) | 2013 | PMID: 23364466 |
Functional associations of genetic variants involved in the clinical manifestation of erythropoietic protoporphyria in the Argentinean population. | Colombo FP | Journal of the European Academy of Dermatology and Venereology : JEADV | 2013 | PMID: 22591014 |
The low expression allele (IVS3-48C) of the ferrochelatase gene leads to low enzyme activity associated with erythropoietic protoporphyria. | Tahara T | International journal of hematology | 2010 | PMID: 21132468 |
Molecular epidemiology of erythropoietic protoporphyria in the U.K. | Whatley SD | The British journal of dermatology | 2010 | PMID: 20105171 |
Biochemical and molecular diagnosis of erythropoietic protoporphyria in an Ashkenazi Jewish family. | Schneider-Yin X | Journal of inherited metabolic disease | 2008 | PMID: 18758989 |
Clinical, biochemical, and genetic study of 11 patients with erythropoietic protoporphyria including one with homozygous disease. | Herrero C | Archives of dermatology | 2007 | PMID: 17875872 |
Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria. | Saruwatari H | The Journal of dermatology | 2006 | PMID: 16958804 |
Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria. | Gouya L | American journal of human genetics | 2006 | PMID: 16385445 |
Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias. | Gouya L | Human genetics | 2004 | PMID: 14669009 |
The penetrance of dominant erythropoietic protoporphyria is modulated by expression of wildtype FECH. | Gouya L | Nature genetics | 2002 | PMID: 11753383 |
The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria. | Nakahashi Y | Proceedings of the National Academy of Sciences of the United States of America | 1992 | PMID: 1729699 |
click to load more click to collapse |
Text-mined citations for rs2272783 ...
HelpRecord last updated May 19, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.