Variant 3-52401844-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004656.4(BAP1):c.*444C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 292,396 control chromosomes in the GnomAD database, including 284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 143 hom., cov: 33)

Exomes 𝑓: 0.040 ( 141 hom. )

Consequence

BAP1
NM_004656.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.271

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]

BAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-52401844-G-A is Benign according to our data. Variant chr3-52401844-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 346111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0361 (5493/152308) while in subpopulation NFE AF= 0.0497 (3377/68012). AF 95% confidence interval is 0.0483. There are 143 homozygotes in gnomad4. There are 2529 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5493 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAP1	NM_004656.4 linkuse as main transcript	c.*444C>T		3_prime_UTR_variant	17/17	ENST00000460680.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BAP1	ENST00000460680.6 linkuse as main transcript	c.*444C>T		3_prime_UTR_variant	17/17	1	NM_004656.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0361

AC:

5492

AN:

152190

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.0217

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0421

GnomAD4 exome

AF:

0.0402

AC:

5638

AN:

140088

Hom.:

141

Cov.:

AF XY:

0.0396

AC XY:

2709

AN XY:

68426

show subpopulations

Gnomad4 AFR exome

AF:

0.0150

Gnomad4 AMR exome

AF:

0.0435

Gnomad4 ASJ exome

AF:

0.0310

Gnomad4 EAS exome

AF:

0.0150

Gnomad4 SAS exome

AF:

0.0157

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0489

Gnomad4 OTH exome

AF:

0.0504

GnomAD4 genome

AF:

0.0361

AC:

5493

AN:

152308

Hom.:

143

Cov.:

AF XY:

0.0340

AC XY:

2529

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.0470

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.0214

Gnomad4 SAS

AF:

0.0213

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0497

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0493

Hom.:

208

Bravo

AF:

0.0371

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2019	- -

BAP1-related tumor predisposition syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.80

DANN

Benign

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over