rs564875789
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The ENST00000460680.6(BAP1):c.375+12T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,613,380 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 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000081 ( 1 hom. )
Consequence
BAP1
ENST00000460680.6 intron
ENST00000460680.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.565
Genes affected
BAP1 (HGNC:950): (BRCA1 associated protein 1) This gene belongs to the ubiquitin C-terminal hydrolase subfamily of deubiquitinating enzymes that are involved in the removal of ubiquitin from proteins. The encoded enzyme binds to the breast cancer type 1 susceptibility protein (BRCA1) via the RING finger domain of the latter and acts as a tumor suppressor. In addition, the enzyme may be involved in regulation of transcription, regulation of cell cycle and growth, response to DNA damage and chromatin dynamics. Germline mutations in this gene may be associated with tumor predisposition syndrome (TPDS), which involves increased risk of cancers including malignant mesothelioma, uveal melanoma and cutaneous melanoma. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 3-52407946-A-T is Benign according to our data. Variant chr3-52407946-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 490862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000788 (12/152364) while in subpopulation SAS AF= 0.00228 (11/4830). AF 95% confidence interval is 0.00128. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 12 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.375+12T>A | intron_variant | ENST00000460680.6 | NP_004647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.375+12T>A | intron_variant | 1 | NM_004656.4 | ENSP00000417132 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000788 AC: 12AN: 152246Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000195 AC: 49AN: 251068Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135774
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GnomAD4 exome AF: 0.0000815 AC: 119AN: 1461016Hom.: 1 Cov.: 32 AF XY: 0.000125 AC XY: 91AN XY: 726810
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GnomAD4 genome AF: 0.0000788 AC: 12AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74502
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
BAP1-related tumor predisposition syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Melanoma, uveal, susceptibility to, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Feb 28, 2017 | - - |
Computational scores
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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