rs149499021
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_004656.4(BAP1):c.2057-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00756 in 1,567,172 control chromosomes in the GnomAD database, including 60 homozygotes. 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, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.2057-4G>T | splice_region_variant, intron_variant | Intron 16 of 16 | ENST00000460680.6 | NP_004647.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00491 AC: 748AN: 152214Hom.: 8 Cov.: 33
GnomAD3 exomes AF: 0.00454 AC: 803AN: 176894Hom.: 2 AF XY: 0.00471 AC XY: 447AN XY: 94842
GnomAD4 exome AF: 0.00785 AC: 11102AN: 1414840Hom.: 52 Cov.: 32 AF XY: 0.00783 AC XY: 5486AN XY: 700206
GnomAD4 genome AF: 0.00491 AC: 748AN: 152332Hom.: 8 Cov.: 33 AF XY: 0.00405 AC XY: 302AN XY: 74488
ClinVar
Submissions by phenotype
not specified Benign:6
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
- -
- -
- -
- -
- -
not provided Uncertain:1Benign:4
- -
- -
- -
- -
BAP1: BP4, BS2 -
BAP1-related tumor predisposition syndrome Benign:4
- -
- -
- -
This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
Hereditary cancer-predisposing syndrome Benign:3
- -
- -
This alteration is classified as 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. -
Melanoma, uveal, susceptibility to, 2 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at