3-52401124-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004656.4(BAP1):​c.*1164G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 232,822 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00071 ( 0 hom. )

Consequence

BAP1
NM_004656.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.209
Variant links:
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 3-52401124-C-G is Benign according to our data. Variant chr3-52401124-C-G is described in ClinVar as [Benign]. Clinvar id is 346103.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00286 (436/152370) while in subpopulation AFR AF= 0.00988 (411/41588). AF 95% confidence interval is 0.00909. There are 1 homozygotes in gnomad4. There are 207 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 436 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BAP1NM_004656.4 linkuse as main transcriptc.*1164G>C 3_prime_UTR_variant 17/17 ENST00000460680.6 NP_004647.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BAP1ENST00000460680.6 linkuse as main transcriptc.*1164G>C 3_prime_UTR_variant 17/171 NM_004656.4 ENSP00000417132 P1
BAP1ENST00000469613.5 linkuse as main transcriptc.*1164G>C 3_prime_UTR_variant 5/51 ENSP00000418320
BAP1ENST00000296288.9 linkuse as main transcriptc.*1164G>C 3_prime_UTR_variant 17/175 ENSP00000296288

Frequencies

GnomAD3 genomes
AF:
0.00279
AC:
425
AN:
152252
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00287
GnomAD4 exome
AF:
0.000708
AC:
57
AN:
80452
Hom.:
0
Cov.:
0
AF XY:
0.000809
AC XY:
30
AN XY:
37090
show subpopulations
Gnomad4 AFR exome
AF:
0.00812
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00258
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000401
Gnomad4 OTH exome
AF:
0.00165
GnomAD4 genome
AF:
0.00286
AC:
436
AN:
152370
Hom.:
1
Cov.:
33
AF XY:
0.00278
AC XY:
207
AN XY:
74522
show subpopulations
Gnomad4 AFR
AF:
0.00988
Gnomad4 AMR
AF:
0.000457
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00284
Bravo
AF:
0.00318
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
0.073
DANN
Benign
0.51
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376927338; hg19: chr3-52435140; API