Variant chr13-46073959-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001872.5(CPB2):c.505G>A(p.Ala169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,578,308 control chromosomes in the GnomAD database, including 83,515 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.34 ( 9111 hom., cov: 30)

Exomes 𝑓: 0.32 ( 74404 hom. )

Consequence

CPB2
NM_001872.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.748

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023388267).

BP6

Variant 13-46073959-C-T is Benign according to our data. Variant chr13-46073959-C-T is described in ClinVar as [Benign]. Clinvar id is 3059667.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 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.505G>A	p.Ala169Thr	missense_variant	6/11	ENST00000181383.10
CPB2-AS1	NR_046226.1 linkuse as main transcript	n.119-20894C>T		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.505G>A	p.Ala169Thr	missense_variant	6/11	1	NM_001872.5	P1	Q96IY4-1
CPB2-AS1	ENST00000663159.1 linkuse as main transcript	n.469+20994C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.343

AC:

51867

AN:

151216

Hom.:

9105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.250

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.344

GnomAD3 exomes

AF:

0.312

AC:

78096

AN:

250340

Hom.:

12551

AF XY:

0.308

AC XY:

41595

AN XY:

135262

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.356

Gnomad EAS exome

AF:

0.258

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.399

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.319

AC:

455760

AN:

1426978

Hom.:

74404

Cov.:

AF XY:

0.316

AC XY:

223469

AN XY:

706124

show subpopulations

Gnomad4 AFR exome

AF:

0.390

Gnomad4 AMR exome

AF:

0.290

Gnomad4 ASJ exome

AF:

0.348

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.324

Gnomad4 OTH exome

AF:

0.320

GnomAD4 genome

AF:

0.343

AC:

51903

AN:

151330

Hom.:

9111

Cov.:

AF XY:

0.343

AC XY:

25377

AN XY:

73894

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.207

Gnomad4 FIN

AF:

0.399

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.344

Alfa

AF:

0.326

Hom.:

18291

Bravo

AF:

0.337

TwinsUK

AF:

0.316

AC:

1172

ALSPAC

AF:

0.332

AC:

1278

ESP6500AA

AF:

0.389

AC:

1714

ESP6500EA

AF:

0.323

AC:

2782

ExAC

AF:

0.310

AC:

37644

Asia WGS

AF:

0.264

AC:

917

AN:

3478

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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.3

DANN

Benign

0.78

DEOGEN2

Benign

0.047

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00088

LIST_S2

Benign

0.040

.;T;T

MetaRNN

Benign

0.0023

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.0

N;N;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

0.61

.;N;N

REVEL

Benign

0.024

Sift

Benign

0.61

.;T;T

Sift4G

Benign

0.68

.;T;T

Polyphen

0.0

B;B;.

Vest4

0.0090, 0.050

MPC

0.37

ClinPred

0.0018

GERP RS

2.7

Varity_R

0.15

gMVP

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