rs374362388
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_032043.3(BRIP1):c.2232C>T(p.Asp744=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000607 in 1,613,654 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000061 ( 1 hom. )
Consequence
BRIP1
NM_032043.3 synonymous
NM_032043.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0490
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 17-61744457-G-A is Benign according to our data. Variant chr17-61744457-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 182353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-61744457-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.049 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2232C>T | p.Asp744= | synonymous_variant | 15/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2232C>T | p.Asp744= | synonymous_variant | 15/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000593 AC: 9AN: 151898Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000107 AC: 27AN: 251238Hom.: 1 AF XY: 0.0000810 AC XY: 11AN XY: 135786
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GnomAD4 exome AF: 0.0000609 AC: 89AN: 1461640Hom.: 1 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727124
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GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74308
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:14
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Feb 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 30, 2014 | 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. - |
Benign, no assertion criteria provided | curation | Leiden Open Variation Database | Aug 13, 2019 | Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 09, 2016 | Variant summary: The c.2232C>T (p.Asp744=) in BRIP1 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00009 (11/121376 chrs tested), predominantly in individuals of Latino origin (0.0004; 5/11574 chrs). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant in this gene (0.00006), suggesting that it is a benign polymorphism. The variant of interest has been cited as Benign by multiple reputable databases/clinical laboratories. Taking together, the variant was classified as Benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 25, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 20, 2017 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 27, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 18, 2014 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial cancer of breast Benign:2
Benign, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Feb 28, 2023 | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. - |
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Breast and/or ovarian cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Feb 23, 2023 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Neoplasm of ovary Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Sep 26, 2016 | - - |
Fanconi anemia complementation group J Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Sep 26, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at