ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.3083G>A (p.Arg1028His) (rs80357459)

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Total submissions: 14
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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) RCV000031088 SCV000244332 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 = 0.00000998
Invitae RCV000588855 SCV000076080 benign not provided 2019-03-05 criteria provided, single submitter clinical testing
GeneDx RCV000120292 SCV000108664 likely benign not specified 2018-01-09 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 RCV000129147 SCV000183868 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Counsyl RCV000031088 SCV000220927 likely benign Breast-ovarian cancer, familial 1 2014-12-01 criteria provided, single submitter literature only
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000048067 SCV000297226 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-12-03 criteria provided, single submitter clinical testing
Color RCV000129147 SCV000537499 likely benign Hereditary cancer-predisposing syndrome 2015-04-06 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000120292 SCV000591424 benign not specified 2012-11-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588855 SCV000699002 benign not provided 2016-03-24 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a missense change involving a non-conserved nucleotide with 3/4 in silico programs predicting a "benign" outcome (SNPs&GO not captured here due to low reliability index). The variant of interest was observed in a large, broad control population, ExAC with an overall allele frequency of 21/121360 (1/5780), however, the variant is predominantly observed in the Latino population with an allele frequency of 19/11576 (1/609), which exceeds the maximum expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Therefore, suggesting that the variant of interest is a common polymorphism specifically found in population(s) of Latino origin. In addition, the variant of interest has been found in affected individuals, with limited co-occurrence and co-segregation information but has been observed to co-occur with another BRCA1 variant, c.5165C>T (p.Ser1722Phe), which was previously classified as VUS-possibly pathogenic and with a pathogenic BRCA2 variant c.771_775delTCAAA p.Asn257_Arg259fs indicating neutrality. Furthermore, the variant of interest has been classified by multiple reputable databases and clinical laboratories via ClinVar, along with publications, Easton_2007 and Lindor_2012, all which classify the variant as "neutral/likely neutral." Therefore, taking all available lines of evidence, the variant of interest is classified as Benign.
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000129147 SCV000803150 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000588855 SCV000806928 likely benign not provided 2018-01-11 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031088 SCV000053684 benign Breast-ovarian cancer, familial 1 2006-10-03 no assertion criteria provided clinical testing
ITMI RCV000120292 SCV000084444 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000031088 SCV000144630 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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