ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.4675+1G>A (rs80358044)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
A.C.Camargo Cancer Center / LGBM, A.C.Camargo Cancer Center RCV000414441 SCV000492461 pathogenic Neoplasm of the breast criteria provided, single submitter research
Ambry Genetics RCV000131822 SCV000186877 pathogenic Hereditary cancer-predisposing syndrome 2018-02-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification,Functionally-validated splicing mutation,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity
Breast Cancer Information Core (BIC) (BRCA1) RCV000077582 SCV000145144 pathogenic Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131822 SCV000911174 pathogenic Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000077582 SCV000326016 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077582 SCV000244367 pathogenic Breast-ovarian cancer, familial 1 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 1
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735555 SCV000863693 likely pathogenic Breast and/or ovarian cancer 2010-10-26 no assertion criteria provided clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762997 SCV000893442 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial 1; Pancreatic cancer 4; FANCONI ANEMIA, COMPLEMENTATION GROUP S 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000048623 SCV000210184 pathogenic not provided 2018-11-13 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA1 c.4675+1G>A or IVS14+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 14 of the BRCA1 gene. This variant is also known as IVS15+1G>A or 4794+1G>A using alternate nomenclature. The variant destroys a canonical splice site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. Functional analyses demonstrate skipping of exon 14 (exon 15 using alternate nomenclature), resulting in multiple aberrant transcripts (Machackova 2008, Steffensen 2014). In addition, BRCA1 c.4675+1G>A has been reported in association with hereditary breast and/or ovarian cancer (Adem 2003, Gutierrez Espeleta 2012, Meisel 2017). We therefore consider this variant to be pathogenic.
Invitae RCV000225764 SCV000076636 pathogenic Hereditary breast and ovarian cancer syndrome 2018-11-16 criteria provided, single submitter clinical testing This sequence change affects a consensus donor splice site in intron 14. It is expected to disrupt mRNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 12491499, 21324516, 23767878, 24884479). In the literature, this variant is also known as IVS15+1G>A and 4794+1G>A. ClinVar contains an entry for this variant (Variation ID: 55256). Experimental studies have shown that this variant results in aberrant splicing (PMID: 21394826, 18489799). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000225764 SCV000839229 pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000048623 SCV000296399 pathogenic not provided 2015-10-15 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000225764 SCV000587418 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000077582 SCV000109385 pathogenic Breast-ovarian cancer, familial 1 2010-07-21 no assertion criteria provided clinical testing

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