rs771441619
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_004656.4(BAP1):c.1117-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004656.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.1117-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.1117-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004656.4 | P1 | |||
BAP1 | ENST00000296288.9 | c.1063-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | |||||
BAP1 | ENST00000490804.1 | n.545-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000820 AC: 2AN: 243902Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132344
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460318Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726316
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2016 | The c.1117-5C>T intronic variant results from a C to T substitution 5 nucleotides upstream from coding exon 12 in the BAP1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.006% (greater than 15000 alleles tested) in our clinical cohort. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor/donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
BAP1-related tumor predisposition syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at