rs573678535
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_004656.4(BAP1):c.581-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,566,216 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000044 ( 2 hom. )
Consequence
BAP1
NM_004656.4 splice_polypyrimidine_tract, intron
NM_004656.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.491
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=-0.79).
BP6
?
Variant 3-52406923-A-G is Benign according to our data. Variant chr3-52406923-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 490872.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000438 (62/1413910) while in subpopulation SAS AF= 0.000732 (59/80582). AF 95% confidence interval is 0.000582. There are 2 homozygotes in gnomad4_exome. There are 49 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 5 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 | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.581-16T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.581-16T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004656.4 | P1 | |||
BAP1 | ENST00000296288.9 | c.581-16T>C | splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
BAP1 | ENST00000471532.5 | n.296-16T>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 | |||||
BAP1 | ENST00000483984.5 | n.438-16T>C | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000798 AC: 14AN: 175434Hom.: 0 AF XY: 0.000139 AC XY: 13AN XY: 93200
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GnomAD4 exome AF: 0.0000439 AC: 62AN: 1413910Hom.: 2 Cov.: 32 AF XY: 0.0000701 AC XY: 49AN XY: 698862
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74480
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
BAP1-related tumor predisposition syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 03, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 25, 2017 | - - |
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