ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3823A>G (p.Ile1275Val) (rs80357280)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000162522 SCV000212917 benign Hereditary cancer-predisposing syndrome 2014-11-18 criteria provided, single submitter clinical testing
Biesecker Lab/Human Development Section,National Institutes of Health RCV000034745 SCV000043163 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000031130 SCV000144888 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing
Color RCV000162522 SCV000910633 benign Hereditary cancer-predisposing syndrome 2015-11-30 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031130 SCV000744622 benign Breast-ovarian cancer, familial 1 2015-09-21 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000195318 SCV000258061 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-02-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000034745 SCV000224999 uncertain significance not provided 2015-04-22 criteria provided, single submitter clinical testing
GeneDx RCV000120279 SCV000209962 likely benign not specified 2018-01-19 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000031130 SCV000743399 benign Breast-ovarian cancer, familial 1 2017-07-28 criteria provided, single submitter clinical testing
ITMI RCV000120279 SCV000084431 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000034745 SCV000699076 likely benign not provided 2017-08-03 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3823A>G (p.Ile1275Val) variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. 2/5 splice prediction tools predict no significant impact on normal splicing, with multiple functional studies supporting these predictions (Anczukow_2008 and Caux-Moncoutier_2009). This variant was found in 42/276872 control chromosomes, predominantly observed in the Latino cohort at a frequency of 0.000872 (30/34414). This frequency is comparable to the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005), suggesting this variant could be a rare benign polymorphism found predominantly in population(s) of Latino origin. Multiple publications have cited the variant in affected individuals with limited information (ie, lack of co-occurrence and co-segregation data)( Zhang _2015, Fernandes _2016, Dean_ 2015). However, reputable databases have cited this variant to co-occur with the BRCA2 c.8364G>A (p.Trp2788X) and c.3922G>T (p.Glu1308X) pathogenic variants, therefore suggesting the variant is in the benign spectrum. In addition, multiple publications, reputable databases, and clinical diagnostic laboratories classify the variant as "likely benign/benign." Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as "likely benign."
Invitae RCV000195318 SCV000076359 benign Hereditary breast and ovarian cancer syndrome 2018-01-10 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031130 SCV000053729 benign Breast-ovarian cancer, familial 1 2008-11-12 no assertion criteria provided clinical testing

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