ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1511G>A (p.Arg504His) (rs56272539)

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Total submissions: 11
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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 RCV000590149 SCV000075520 benign not provided 2019-03-03 criteria provided, single submitter clinical testing
CSER_CC_NCGL; University of Washington Medical Center 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
Counsyl RCV000111637 SCV000220533 likely benign Breast-ovarian cancer, familial 1 2014-07-22 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America 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 RCV000162973 SCV000902715 benign Hereditary cancer-predisposing syndrome 2016-11-15 criteria provided, single submitter clinical testing
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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