ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.670+16G>A (rs199916228)

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Total submissions: 7
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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) RCV001003384 SCV001161593 benign Breast-ovarian cancer, familial 1 2019-06-18 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 = 1.35E-06
Ambry Genetics RCV000131335 SCV000186309 likely benign Hereditary cancer-predisposing syndrome 2015-08-05 criteria provided, single submitter clinical testing
GeneDx RCV000444606 SCV000512281 benign not specified 2015-05-07 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.
Invitae RCV001079367 SCV000560302 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000444606 SCV000591292 likely benign not specified 2016-06-29 criteria provided, single submitter clinical testing
Color RCV000131335 SCV000683342 likely benign Hereditary cancer-predisposing syndrome 2017-01-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587845 SCV000699285 likely benign not provided 2017-02-13 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.670+16G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. This variant was found in 5/103692 control chromosomes at a frequency of 0.0000482, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). However, this variant, which is found in 11 patients in the UMD database and 2 families in kConFab, is reported as co-occurring with a pathogenic variant in BRCA2 (c.7795_7797delGAA (p.Glu2599del)). Multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/polymorphysm". Similarly, 4/5 in silico tools (via Alamut) predict that this variant does not affect the normal splicing pattern and in functional studies the variant was shown to increase exon 10 inclusion (Steffensen_EJHG_2014). Taken together, this data strongly support non-pathogenicity, therefore the variant was classified as likely benign.

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