rs1555572620
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_032043.3(BRIP1):c.3411_3412delinsCT(p.Asp1138Tyr) variant causes a missense change. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. YD1137YN) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 31)
Consequence
BRIP1
NM_032043.3 missense
NM_032043.3 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.3411_3412delinsCT | p.Asp1138Tyr | missense_variant | 20/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.3411_3412delinsCT | p.Asp1138Tyr | missense_variant | 20/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2022 | The c.3411_3412delTGinsCT variant (also known as p.D1138Y), located in coding exon 19 of the BRIP1 gene, results from an in-frame deletion of TG and insertion of CT at nucleotide positions 3411 to 3412. This results in the substitution of the aspartic acid residue for a tyrosine residue at codon 1138, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 02, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jul 21, 2022 | Variant summary: BRIP1 c.3411_3412delinsCT (p.Asp1138Tyr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of at least 5.3e-05 in 150918 control chromosomes (gnomAD v3.1.2). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. p.Asp1138Tyr has been reported in the literature in individuals being tested for or affected with cancer, including Lynch syndrome and Hereditary Breast And Ovarian Cancer Syndrome (e.g. Mauer_2013, Lu_2015, Yurgelun_2015). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Breast and/or ovarian cancer Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 23, 2023 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 1138 of the BRIP1 protein (p.Asp1138Tyr). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with breast cancer (PMID: 24113346). ClinVar contains an entry for this variant (Variation ID: 570962). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at