Variant 13-46067346-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001872.5(CPB2):c.663A>G(p.Pro221=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,583,384 control chromosomes in the GnomAD database, including 448,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.79 ( 47659 hom., cov: 32)

Exomes 𝑓: 0.75 ( 400543 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.66

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 13-46067346-T-C is Benign according to our data. Variant chr13-46067346-T-C is described in ClinVar as [Benign]. Clinvar id is 3060410.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 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.663A>G	p.Pro221=	synonymous_variant	7/11	ENST00000181383.10
CPB2-AS1	NR_046226.1 linkuse as main transcript	n.118+14381T>C		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.663A>G	p.Pro221=	synonymous_variant	7/11	1	NM_001872.5	P1	Q96IY4-1
CPB2-AS1	ENST00000663159.1 linkuse as main transcript	n.469+14381T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119867

AN:

152020

Hom.:

47613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.878

Gnomad AMI

AF:

0.663

Gnomad AMR

AF:

0.777

Gnomad ASJ

AF:

0.705

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.814

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.743

Gnomad OTH

AF:

0.751

GnomAD3 exomes

AF:

0.765

AC:

191960

AN:

250768

Hom.:

73869

AF XY:

0.757

AC XY:

102651

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.699

Gnomad EAS exome

AF:

0.828

Gnomad SAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.816

Gnomad NFE exome

AF:

0.736

Gnomad OTH exome

AF:

0.752

GnomAD4 exome

AF:

0.746

AC:

1067777

AN:

1431246

Hom.:

400543

Cov.:

AF XY:

0.744

AC XY:

531151

AN XY:

713736

show subpopulations

Gnomad4 AFR exome

AF:

0.879

Gnomad4 AMR exome

AF:

0.813

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.846

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.737

Gnomad4 OTH exome

AF:

0.743

GnomAD4 genome

AF:

0.789

AC:

119969

AN:

152138

Hom.:

47659

Cov.:

AF XY:

0.790

AC XY:

58795

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.878

Gnomad4 AMR

AF:

0.776

Gnomad4 ASJ

AF:

0.705

Gnomad4 EAS

AF:

0.820

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.814

Gnomad4 NFE

AF:

0.743

Gnomad4 OTH

AF:

0.752

Alfa

AF:

0.746

Hom.:

55953

Bravo

AF:

0.789

Asia WGS

AF:

0.775

AC:

2693

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CPB2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 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

-0.93

Cadd

Benign

0.025

Dann

Benign

0.45

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