ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3636A>G (p.Ser1212=) (rs148038877)

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Total submissions: 6
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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) RCV000494812 SCV000578220 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02;
GeneDx RCV000123913 SCV000167295 benign not specified 2014-02-24 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 RCV000163075 SCV000213574 likely benign Hereditary cancer-predisposing syndrome 2014-10-08 criteria provided, single submitter clinical testing
Invitae RCV000588372 SCV000253501 likely benign not provided 2019-02-18 criteria provided, single submitter clinical testing
Color RCV000163075 SCV000688443 likely benign Hereditary cancer-predisposing syndrome 2016-08-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588372 SCV000699048 likely benign not provided 2016-08-28 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.3636A>G (p.Ser1212Ser) variant causes a synonymous change involving a non-conserved nucleotide with 4/5 splice prediction tools predict no significant impact on splicing. A functional study by minigene assay reports that it was one of the variants that did not dramatically alter splicing through disruption of an ESE (Anczukow_2008). The exact extent of functional impairment was not provided in the study. The variant of interest was found in controls with an allele frequency of 1/121208, which does not exceed the maximum expected allele frequency for a pathogenic BRCA1 variant (1/1000). It has also been reported in individuals from HBOC families (Judkins_2005, Anczukow_2008); however with limited information (i.e. no co-occurrence and cosegregation data provided). Multiple clinical laboratories and reputable databases cite the variant as "likely benign/benign." Therefore, taken all available lines of evidence into consideration, the variant of interest has been classified as likely benign until additional information becomes available.

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