ClinVar Miner

Submissions for variant NM_007299.4(BRCA1):c.571G>A (p.Val191Ile) (rs80357090)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031265 SCV000244408 benign 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 1 based on posterior probability = 0.000000157
Invitae RCV000586929 SCV000077076 benign not provided 2019-03-04 criteria provided, single submitter clinical testing
GeneDx RCV000123886 SCV000167231 benign not specified 2013-12-16 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000162499 SCV000212887 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Pathway Genomics RCV000031265 SCV000223750 likely benign Breast-ovarian cancer, familial 1 2014-10-30 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000123886 SCV000591287 benign not specified 2014-01-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000586929 SCV000602666 benign not provided 2017-10-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586929 SCV000699276 benign not provided 2016-03-28 criteria provided, single submitter clinical testing Variant Summary: The variant of interest causes a missense change involving a non-conserved nucleotide with 3/4 in silico programs (SNPs&GO not captured here due to low reliability index) predict a "benign" outcome. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 36/121098 (1/3363), predominantly in the East Asian cohort, 29/8636 (1/297), which exceeds the predicted maximum expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Therefore, suggesting that the variant of interest is a polymorphism found in population(s) of East Asian origin. The variant of interest has been reported in multiple affected individuals via publications and databases including multiple reported co-occurrences with a pathogenic BRCA1 variant, c.181T>G (p.Cys61Gly classified as pathogenic by LCA) and c.188T>A (p.L63X), and a pathogenic BRCA2 variant, c.9382C>T (p.R3128X). Functional studies show that the variant acts comparable to wild type function (Bouwman_2013, Lu_2015). In addition, multiple reputable clinical laboratories cite the variant with a classification of "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Benign.
PreventionGenetics,PreventionGenetics RCV000123886 SCV000806978 benign not specified 2017-03-20 criteria provided, single submitter clinical testing
Color RCV000162499 SCV000910664 benign Hereditary cancer-predisposing syndrome 2016-01-22 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031265 SCV000053870 benign Breast-ovarian cancer, familial 1 2008-09-16 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031265 SCV000145630 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031265 SCV000733668 benign Breast-ovarian cancer, familial 1 no assertion criteria provided clinical testing

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