ClinVar Miner

Submissions for variant NM_007299.4(BRCA1):c.593+3G>A (rs80358013)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159866 SCV000209915 benign not specified 2014-08-29 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 RCV000166105 SCV000216872 likely benign Hereditary cancer-predisposing syndrome 2018-11-05 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000159866 SCV000494426 likely benign not specified 2019-09-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.593+3G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. This prediction has been confirmed by a functional study (Leman_2018). The variant allele was found at a frequency of 2.8e-05 in 251310 control chromosomes, predominantly within the African or African-American subpopulation at a frequency of 0.00043 in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.593+3G>A in individuals affected with Hereditary Breast and Ovarian Cancer has been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.2092delC (p.Leu698TyrfsX32), UMD), providing supporting evidence for a benign role. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000416557 SCV000560277 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000159866 SCV000602677 likely benign not specified 2016-09-15 criteria provided, single submitter clinical testing
Counsyl RCV000077174 SCV000785370 likely benign Breast-ovarian cancer, familial 1 2017-07-14 criteria provided, single submitter clinical testing
Color Health, Inc RCV000166105 SCV001358889 likely benign Hereditary cancer-predisposing syndrome 2018-01-29 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077174 SCV000108971 likely benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000077174 SCV000145634 uncertain significance Breast-ovarian cancer, familial 1 1997-11-14 no assertion criteria provided clinical testing

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