3-52401844-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.271

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]

ACMG classification

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 GnomAd at 5492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BAP1	NM_004656.4	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	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.: 33

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.: 0 AF XY: 0.0396 AC XY: 2709 AN XY: 68426

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.: 33 AF XY: 0.0340 AC XY: 2529 AN XY: 74482

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

BAP1-related tumor predisposition syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 15, 2019

- -

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

Other links and lift over

dbSNP: rs123598; hg19: chr3-52435860;