3-52408338-G-C

Variant names:

• chr3-52408338-G-C
• rs123602
• NM_004656.4:c.255+136C>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004656.4(BAP1):​c.255+136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,410,818 control chromosomes in the GnomAD database, including 22,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2900 hom., cov: 32)
  • Exomes 𝑓: 0.17 (19418 hom.)
• Consequence: BAP1 NM_004656.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.915

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=-0.9).
• BP6: Variant 3-52408338-G-C is Benign according to our data. Variant chr3-52408338-G-C is described in ClinVar as [Benign]. Clinvar id is 1252465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BAP1	NM_004656.4	c.255+136C>G		intron_variant	Intron 4 of 16	ENST00000460680.6	NP_004647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BAP1	ENST00000460680.6	c.255+136C>G		intron_variant	Intron 4 of 16	1	NM_004656.4	ENSP00000417132.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27985 AN: 151984 Hom.: 2898 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0302

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.170 AC: 213842 AN: 1258716 Hom.: 19418 AF XY: 0.168 AC XY: 105219 AN XY: 627024

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.126

Gnomad4 ASJ exome AF: 0.152

Gnomad4 EAS exome AF: 0.0245

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0935

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.184 AC: 28004 AN: 152102 Hom.: 2900 Cov.: 32 AF XY: 0.177 AC XY: 13185 AN XY: 74368

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.0299

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0535 Hom.: 59

Bravo AF: 0.192

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.68

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: rs123602; hg19: chr3-52442354;