ClinVar Miner

Submissions for variant NM_032043.2(BRIP1):c.1936-5_1936-4delinsGT (rs587781481)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412672 SCV000150042 uncertain significance not provided 2017-08-17 criteria provided, single submitter clinical testing This variant is denoted BRIP1 c.1936-5_1936-4delTCinsGT or IVS13-5_IVS13-4delTCinsGT and consists of two adjacent nucleotide substitutions at the -5 and -4 positions of intron 13 of the BRIP1 gene. The normal sequence, with the bases that are deleted and inserted in brackets, is atat[deltc][insgt]tagg. Multiple in silico models predict this variant to destroy the nearby natural splice acceptor site, and to possibly cause abnormal gene splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. The nucleotides that are deleted are not conserved across species. Based on the currently available information, we consider BRIP1 c.1936-5_1936-4delTCinsGT to be a variant of uncertain significance.
Ambry Genetics RCV000116133 SCV000184205 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-19 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000205283 SCV000261156 uncertain significance Familial cancer of breast; Fanconi anemia, complementation group J 2019-11-27 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the BRIP1 mRNA. It does not directly change the encoded amino acid sequence of the BRIP1 protein. While this particular variant is not present in population databases (rs587781481, ExAC no frequency), two variants at this position, c.1936-5T>G and c.1936-4C>T, located on the same chromosome (i.e. in phase), are present in population databases (ExAC, 0.03%). This variant has not been reported in the literature, but it has been observed in individuals with personal and/or family histories of breast and prostate cancer (Invitae). ClinVar contains an entry for this variant (Variation ID: 128165). Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Color RCV000116133 SCV000684169 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-30 criteria provided, single submitter clinical testing

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