chr3-52409555-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 3P and 20B. PM1PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_004656.4(BAP1):c.121G>A(p.Gly41Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000368 in 1,614,160 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G41A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004656.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.121G>A | p.Gly41Ser | missense_variant, splice_region_variant | 3/17 | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.121G>A | p.Gly41Ser | missense_variant, splice_region_variant | 3/17 | 1 | NM_004656.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000783 AC: 197AN: 251496Hom.: 1 AF XY: 0.000949 AC XY: 129AN XY: 135922
GnomAD4 exome AF: 0.000384 AC: 562AN: 1461872Hom.: 6 Cov.: 32 AF XY: 0.000485 AC XY: 353AN XY: 727240
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74456
ClinVar
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | May 12, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 2020 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24728327, 23709298, 26166446, 22683710, 26554828, 33240524) - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | Dec 13, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 20, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 28, 2018 | 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 | Dec 05, 2021 | - - |
BAP1-related tumor predisposition syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
BAP1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at