ClinVar Miner

Submissions for variant NM_032043.3(BRIP1):c.3178G>A (p.Val1060Ile)

gnomAD frequency: 0.00001  dbSNP: rs149016505
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534521 SCV000633654 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1060 of the BRIP1 protein (p.Val1060Ile). This variant is present in population databases (rs149016505, gnomAD 0.006%). This missense change has been observed in individual(s) with breast cancer (PMID: 26921362). ClinVar contains an entry for this variant (Variation ID: 461140). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000568104 SCV000661527 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-02 criteria provided, single submitter clinical testing The p.V1060I variant (also known as c.3178G>A), located in coding exon 19 of the BRIP1 gene, results from a G to A substitution at nucleotide position 3178. The valine at codon 1060 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in patients with breast cancer (Tung N et al. Cancer. 2015 Jan;121:25-33; Easton DF et al. J. Med. Genet. 2016 05;53:298-309). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000709530 SCV000839355 uncertain significance Fanconi anemia complementation group J 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000534521 SCV000896647 uncertain significance Familial cancer of breast; Fanconi anemia complementation group J 2018-10-31 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000568104 SCV000911856 uncertain significance Hereditary cancer-predisposing syndrome 2021-01-20 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1060 of the BRIP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 25186627, 26921362). This variant has also been identified in 2/251440 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV000989982 SCV001140744 uncertain significance Familial cancer of breast 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001567722 SCV001791463 uncertain significance not provided 2020-03-09 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer (Easton 2016); This variant is associated with the following publications: (PMID: 26921362)
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV003321649 SCV004026872 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing

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