3-52401314-G-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1
The NM_004656.4(BAP1):c.*974C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 233,480 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.017 ( 64 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 10 hom. )
Consequence
BAP1
NM_004656.4 3_prime_UTR
NM_004656.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.27
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
Variant 3-52401314-G-A is Benign according to our data. Variant chr3-52401314-G-A is described in ClinVar as [Benign]. Clinvar id is 346105.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.*974C>T | 3_prime_UTR_variant | 17/17 | ENST00000460680.6 | NP_004647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.*974C>T | 3_prime_UTR_variant | 17/17 | 1 | NM_004656.4 | ENSP00000417132 | P1 | ||
BAP1 | ENST00000469613.5 | c.*974C>T | 3_prime_UTR_variant | 5/5 | 1 | ENSP00000418320 | ||||
BAP1 | ENST00000296288.9 | c.*974C>T | 3_prime_UTR_variant | 17/17 | 5 | ENSP00000296288 |
Frequencies
GnomAD3 genomes AF: 0.0166 AC: 2520AN: 152228Hom.: 63 Cov.: 33
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GnomAD4 exome AF: 0.00359 AC: 291AN: 81134Hom.: 10 Cov.: 0 AF XY: 0.00305 AC XY: 114AN XY: 37358
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GnomAD4 genome AF: 0.0166 AC: 2523AN: 152346Hom.: 64 Cov.: 33 AF XY: 0.0161 AC XY: 1198AN XY: 74504
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
BAP1-related tumor predisposition syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at