rs199926938
Positions:
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004656.4(BAP1):c.659+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,554,140 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00087 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 4 hom. )
Consequence
BAP1
NM_004656.4 intron
NM_004656.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.659
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 3-52406818-A-G is Benign according to our data. Variant chr3-52406818-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 490873.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 133 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.659+11T>C | intron_variant | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.659+11T>C | intron_variant | 1 | NM_004656.4 | P1 | |||
BAP1 | ENST00000296288.9 | c.659+11T>C | intron_variant | 5 | |||||
BAP1 | ENST00000471532.5 | n.385T>C | non_coding_transcript_exon_variant | 4/5 | 5 | ||||
BAP1 | ENST00000483984.5 | n.527T>C | non_coding_transcript_exon_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000874 AC: 133AN: 152238Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
133
AN:
152238
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000755 AC: 121AN: 160178Hom.: 1 AF XY: 0.000698 AC XY: 59AN XY: 84468
GnomAD3 exomes
AF:
AC:
121
AN:
160178
Hom.:
AF XY:
AC XY:
59
AN XY:
84468
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000319 AC: 447AN: 1401784Hom.: 4 Cov.: 32 AF XY: 0.000289 AC XY: 200AN XY: 691666
GnomAD4 exome
AF:
AC:
447
AN:
1401784
Hom.:
Cov.:
32
AF XY:
AC XY:
200
AN XY:
691666
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000873 AC: 133AN: 152356Hom.: 0 Cov.: 33 AF XY: 0.00129 AC XY: 96AN XY: 74504
GnomAD4 genome
?
AF:
AC:
133
AN:
152356
Hom.:
Cov.:
33
AF XY:
AC XY:
96
AN XY:
74504
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
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 | Invitae | Dec 06, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 09, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at