Genetic Variant CPB2:p.Ile251Ile (chr13-46064691-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

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

The NM_001872.5(CPB2):c.753C>T(p.Ile251Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 1,613,616 control chromosomes in the GnomAD database, including 7,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.094 ( 869 hom., cov: 32)

Exomes 𝑓: 0.079 ( 6179 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.18

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 13-46064691-G-A is Benign according to our data. Variant chr13-46064691-G-A is described in ClinVar as [Benign]. Clinvar id is 3059439.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.18 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPB2	NM_001872.5 link	c.753C>T	p.Ile251Ile	synonymous_variant	Exon 8 of 11	ENST00000181383.10	NP_001863.3	Q96IY4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPB2	ENST00000181383.10 link	c.753C>T	p.Ile251Ile	synonymous_variant	Exon 8 of 11	1	NM_001872.5	ENSP00000181383.4		Q96IY4-1

Frequencies

GnomAD3 genomes

AF:

0.0946

AC:

14390

AN:

152086

Hom.:

871

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0706

Gnomad EAS

AF:

0.287

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0645

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.109

AC:

27302

AN:

251388

Hom.:

2218

AF XY:

0.103

AC XY:

14038

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.0695

Gnomad EAS exome

AF:

0.304

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0949

GnomAD4 exome

AF:

0.0790

AC:

115472

AN:

1461412

Hom.:

6179

Cov.:

AF XY:

0.0791

AC XY:

57521

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.192

Gnomad4 ASJ exome

AF:

0.0700

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0416

Gnomad4 NFE exome

AF:

0.0645

Gnomad4 OTH exome

AF:

0.0915

GnomAD4 genome

AF:

0.0945

AC:

14381

AN:

152204

Hom.:

869

Cov.:

AF XY:

0.0945

AC XY:

7029

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0706

Gnomad4 EAS

AF:

0.286

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0422

Gnomad4 NFE

AF:

0.0645

Gnomad4 OTH

AF:

0.0985

Alfa

AF:

0.0724

Hom.:

629

Bravo

AF:

0.107

Asia WGS

AF:

0.180

AC:

623

AN:

3478

EpiCase

AF:

0.0651

EpiControl

AF:

0.0679

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CPB2-related disorder

Benign:1

Nov 19, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.71

CADD

Benign

0.85

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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