Variant 13-46067331-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001872.5(CPB2):c.678T>C(p.Asp226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,553,388 control chromosomes in the GnomAD database, including 79,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9200 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70087 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.967

Variant links:

Genes affected

CPB2 (HGNC:2300): (carboxypeptidase B2) Carboxypeptidases are enzymes that hydrolyze C-terminal peptide bonds. The carboxypeptidase family includes metallo-, serine, and cysteine carboxypeptidases. According to their substrate specificity, these enzymes are referred to as carboxypeptidase A (cleaving aliphatic residues) or carboxypeptidase B (cleaving basic amino residues). The protein encoded by this gene is activated by trypsin and acts on carboxypeptidase B substrates. After thrombin activation, the mature protein downregulates fibrinolysis. Polymorphisms have been described for this gene and its promoter region. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

CPB2 links:

CPB2-AS1 (HGNC:39898): (CPB2 antisense RNA 1)

CPB2-AS1 links:

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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=-0.5).

BP6

Variant 13-46067331-A-G is Benign according to our data. Variant chr13-46067331-A-G is described in ClinVar as [Benign]. Clinvar id is 3059117.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.967 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPB2	NM_001872.5 linkuse as main transcript	c.678T>C	p.Asp226=	synonymous_variant	7/11	ENST00000181383.10
CPB2-AS1	NR_046226.1 linkuse as main transcript	n.118+14366A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPB2	ENST00000181383.10 linkuse as main transcript	c.678T>C	p.Asp226=	synonymous_variant	7/11	1	NM_001872.5	P1	Q96IY4-1
CPB2-AS1	ENST00000663159.1 linkuse as main transcript	n.469+14366A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

52177

AN:

151950

Hom.:

9194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.288

Gnomad AMR

AF:

0.325

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.205

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.313

AC:

78482

AN:

250670

Hom.:

12676

AF XY:

0.308

AC XY:

41785

AN XY:

135512

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.261

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.312

AC:

436738

AN:

1401320

Hom.:

70087

Cov.:

AF XY:

0.310

AC XY:

217019

AN XY:

700450

show subpopulations

Gnomad4 AFR exome

AF:

0.384

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.315

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.343

AC:

52215

AN:

152068

Hom.:

9200

Cov.:

AF XY:

0.344

AC XY:

25561

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.391

Gnomad4 AMR

AF:

0.325

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.347

Alfa

AF:

0.326

Hom.:

10354

Bravo

AF:

0.338

Asia WGS

AF:

0.262

AC:

912

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CPB2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.0

DANN

Benign

0.56

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