ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3783A>G (p.Leu1261=) (rs80356831)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164014 SCV000214619 likely benign Hereditary cancer-predisposing syndrome 2014-09-09 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112185 SCV000144880 benign Breast-ovarian cancer, familial 1 2004-12-30 no assertion criteria provided clinical testing
Color RCV000164014 SCV000688451 likely benign Hereditary cancer-predisposing syndrome 2017-09-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000422101 SCV000591472 benign not specified 2014-06-25 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112185 SCV000578178 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx RCV000422101 SCV000515622 likely benign not specified 2017-09-29 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.
Integrated Genetics/Laboratory Corporation of America RCV000422101 SCV000918693 likely benign not specified 2018-03-05 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3783A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.4e-05 in 276922 control chromosomes. This frequency is not higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (1.4e-05 vs 0.001), allowing no conclusion about variant significance. The c.3783A>G variant has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about an association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported (BRCA1 c.83_84delTG, p.Leu28ArgfsX12; BRCA2 c.2957insG, p.Asn986ArgfsX2), providing supporting evidence for a benign role. One publication reports experimental evidence evaluating an impact on protein function, which showed no damaging effect from this variant. 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 benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000048332 SCV000076345 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-17 criteria provided, single submitter clinical testing

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