ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1511G>A (p.Arg504His) (rs56272539)

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Total submissions: 13
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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) RCV000111637 SCV000244305 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 = 0.00000106
Invitae RCV001086247 SCV000075520 benign Hereditary breast and ovarian cancer syndrome 2020-11-02 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148409 SCV000190108 uncertain significance Breast and/or ovarian cancer 2014-06-01 criteria provided, single submitter research Low GERP score may suggest that this variant may belong in a lower pathogenicity class
GeneDx RCV000120287 SCV000209928 likely benign not specified 2017-10-30 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 RCV000162973 SCV000213461 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000111637 SCV000220533 likely benign Breast-ovarian cancer, familial 1 2014-07-22 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590149 SCV000698871 benign not provided 2016-03-25 criteria provided, single submitter clinical testing Variant Summary: The c.1511G>A variant involves the alteration of a non-conserved nucleotide and 3/4 in silico tools predict a benign outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.007% (8/121170), which does not exceed the maximal expected allele frequency for a pathogenic variant in BRCA1 (0.10%). However, the frequency data should still suggest that this variant is likely to be a rare polymorphism. The variant has been reported to co-occur with many deleterious pathogenic variants in BRCA1, such as c.70_80del (8 times in BIC), c.78_79insCATCTG (1 time in BIC) and p.Ser510Ter (1 time in BIC). A publication (Tavtigian_2006) also reported co-occurrence with an unspecified deleterious BRCA1 variant in six samples. (Presence of a variant in trans with another deleterious variant in BRCA1 is a definite evidence of benign outcome and thus it is very likely that the reported co-occurrence information is in line with this notion.) Studies presenting multifactorial probability based models report the variant as a neutral variant (Easton_2007, Lindor_2012). In addition, multiple reputable databases/clinical diagnostic laboratories have classified the variant as neutral/likely benign/benign. Taken together, this variant is classified as Benign.
Color Health, Inc RCV000162973 SCV000902715 benign Hereditary cancer-predisposing syndrome 2016-11-15 criteria provided, single submitter clinical testing
Mendelics RCV000111637 SCV001140600 benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000111637 SCV001287422 likely benign Breast-ovarian cancer, familial 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ITMI RCV000120287 SCV000084439 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000111637 SCV000144120 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120287 SCV000587146 benign not specified 2014-01-31 no assertion criteria provided research

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