ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.144G>A (p.Leu48=) (rs151168457)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163861 SCV000214448 likely benign Hereditary cancer-predisposing syndrome 2014-10-05 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001079693 SCV000259826 benign Familial cancer of breast 2020-12-03 criteria provided, single submitter clinical testing
GeneDx RCV000587640 SCV000293279 uncertain significance not provided 2018-08-28 criteria provided, single submitter clinical testing This variant is denoted BARD1 c.144G>A at the DNA level. It is silent at the coding level, preserving a Leucine at codon 48. In-silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. This variant was observed at an allele frequency of 0.11% (25/22,832) in individuals of African ancestry in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether BARD1 c.144G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000163861 SCV000576465 uncertain significance Hereditary cancer-predisposing syndrome 2017-02-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587640 SCV000696743 likely benign not provided 2017-05-15 criteria provided, single submitter clinical testing Variant summary: The BARD1 c.144G>A (p.Leu48Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant and ESE finder predicts that this variant may abrogate the binding sites for SRp55 and SF2/ASF. However, 5/5 splice prediction tools predict no significant impact on normal splicing. These predictions have not been confirmed by functional studies. The variant of interest has been found in large and broad control population from ExAC in 13/107980 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.001326 (10/7544). This frequency is about 6 times the estimated maximal expected allele frequency of a pathogenic BARD1 variant (0.0002188), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, this variant was found to be co-occurring with a pathogenic variant ATM c.7913G>A (p.Trp2638X) in an internal sample, further supporting benign outcome. In ClinVar, while two clinical laboratories classify it as likely benign, one classifies it as uncertain significance. The variant of interest has not been reported in affected individuals via publications. Taken together, this variant is currently classified as Likely Benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587640 SCV000887587 benign not provided 2018-08-20 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163861 SCV000910805 likely benign Hereditary cancer-predisposing syndrome 2016-01-06 criteria provided, single submitter clinical testing

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