rs201617644
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_032043.3(BRIP1):c.297C>T(p.Asp99=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
BRIP1
NM_032043.3 synonymous
NM_032043.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.282
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=-0.9).
BP6
?
Variant 17-61857140-G-A is Benign according to our data. Variant chr17-61857140-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 184212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.282 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.297C>T | p.Asp99= | synonymous_variant | 4/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.297C>T | p.Asp99= | synonymous_variant | 4/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251454Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135896
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461778Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727202
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 10, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | BRIP1: BP4 - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Aug 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 27, 2023 | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 23, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Benign, no assertion criteria provided | research | King Laboratory, University of Washington | Sep 01, 2019 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 20, 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. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Feb 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Dec 13, 2016 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
BRIP1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 13, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Fanconi anemia complementation group J Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Aug 29, 2016 | - - |
Familial cancer of breast Benign:1
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. - |
Ovarian neoplasm Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Aug 29, 2016 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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