ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5153-6C>A (rs80358129)

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Total submissions: 10
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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) RCV000083062 SCV000244389 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 = 0.00000901
GeneDx RCV000159891 SCV000209986 benign not specified 2014-09-09 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.
Invitae RCV001085661 SCV000253510 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000579994 SCV000683264 benign Hereditary cancer-predisposing syndrome 2016-09-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590543 SCV000699215 likely benign not provided 2017-02-23 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.5153-6C>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool, Mutation Taster, predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE Finder predicts the disruption of an SC35 ESE site caused by the variant. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/119890 control chromosomes at a frequency of 0.0000334, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign or benign. Two publications have shown that the variant does not affect splicing or exon skipping using in vitro splicing assays. In addition, 3 different publications used probability modeling and prediction tools to analyze the effect of the variant on splicing with conflicting results; 2 studies predicted no significant effect, and 1 predicted an alteration in splicing due to the variant. Taken together, this variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590543 SCV000888937 likely benign not provided 2020-02-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083062 SCV000115136 likely benign Breast-ovarian cancer, familial 1 2009-01-02 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083062 SCV000145358 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000083062 SCV001241799 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro
Human Genetics - Radboudumc,Radboudumc RCV000590543 SCV001956793 likely benign not provided no assertion criteria provided clinical testing

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