ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1459G>T (p.Val487Phe) (rs369588942)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130777 SCV000185670 likely benign Hereditary cancer-predisposing syndrome 2019-12-04 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
GeneDx RCV000159870 SCV000209926 likely benign not specified 2018-01-11 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.
Counsyl RCV000030995 SCV000488281 uncertain significance Breast-ovarian cancer, familial 1 2016-02-12 criteria provided, single submitter clinical testing
Invitae RCV000459454 SCV000549307 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000159870 SCV000698866 likely benign not specified 2021-04-02 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1459G>T (p.Val487Phe) results in a non-conservative amino acid change located in the BRCA1, serine-rich domain (IPR025994) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251284 control chromosomes, predominantly at a frequency of 0.00062 within the African or African-American subpopulation in the gnomAD database. This frequency is only slightly lower than estimated for a pathogenic variant in BRCA1 causing Hereditary Breast And Ovarian Cancer Syndrome (0.00062 vs 0.001), suggesting that the variant could be a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1459G>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (VUS, n=2; likely benign, n=5). Based on the emerging majority consensus among peers and the evidence outlined above, the variant was classified as likely benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000586346 SCV000859165 uncertain significance not provided 2018-01-09 criteria provided, single submitter clinical testing
Color Health, Inc RCV000130777 SCV000909382 likely benign Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000586346 SCV001133488 likely benign not provided 2019-11-15 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000030995 SCV000053587 likely benign Breast-ovarian cancer, familial 1 2010-09-03 no assertion criteria provided clinical testing

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