ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1427A>G (p.His476Arg) (rs55720177)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000167831 SCV000075486 benign Hereditary breast and ovarian cancer syndrome 2017-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130932 SCV000185844 likely benign Hereditary cancer-predisposing syndrome 2017-09-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Co-occurence with mutation in same gene (phase unknown),Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
GeneDx RCV000120270 SCV000209924 likely benign not specified 2018-02-14 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 RCV000111616 SCV000220997 likely benign Breast-ovarian cancer, familial 1 2014-12-30 criteria provided, single submitter literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000120270 SCV000600250 likely benign not specified 2017-03-17 criteria provided, single submitter clinical testing
Color RCV000130932 SCV000682961 likely benign Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589279 SCV000698865 benign not provided 2017-08-07 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1427A>G (p.His476Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide located in the BRCA1, serine-rich domain (IPR025994) (InterPro). 3/5 in silico tools predict a damaging outcome for this variant. A functional study showed no dramatic effect on splicing for this variant (Anczukow_Genes Chromosomes and Cancer_2008). This variant was found in 34/121588 control chromosomes in the control population ExAc and in published studies, predominantly observed in the African subpopulation at a frequency of 0.00298 (31/10404). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has been reported in affected individuals via publications including one paper reporting the variant to co-occur with another deleterious BRCA1 variant, c.943ins10 (Judkins_2005) referenced in BIC, which also reports another individual with a co-occurring deleterious BRCA2 variant, c.5616_5620delAGTAA. This variant is found in two internal specimens co-occuring with pathogenic variants BRCA2 c.2957_2958insG and PMS2 c.2186_2187delTC. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589279 SCV000887624 benign not provided 2018-04-24 criteria provided, single submitter clinical testing
ITMI RCV000120270 SCV000084422 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA1) RCV000111616 SCV000144092 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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