Variant chr13-46082534-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.291T>C(p.Asp97=) 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 1,609,964 control chromosomes in the GnomAD database, including 455,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.78 ( 46948 hom., cov: 31)

Exomes 𝑓: 0.75 ( 408263 hom. )

Consequence

CPB2
NM_001872.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.01

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=-0.59).

BP6

Variant 13-46082534-A-G is Benign according to our data. Variant chr13-46082534-A-G is described in ClinVar as [Benign]. Clinvar id is 3060878.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 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.291T>C	p.Asp97=	synonymous_variant	4/11	ENST00000181383.10
CPB2-AS1	NR_046226.1 linkuse as main transcript	n.119-12319A>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.291T>C	p.Asp97=	synonymous_variant	4/11	1	NM_001872.5	P1	Q96IY4-1
CPB2-AS1	ENST00000663159.1 linkuse as main transcript	n.469+29569A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.783

AC:

119045

AN:

151998

Hom.:

46911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.860

Gnomad AMI

AF:

0.660

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.713

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.744

GnomAD3 exomes

AF:

0.764

AC:

191814

AN:

251136

Hom.:

73584

AF XY:

0.756

AC XY:

102590

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.864

Gnomad AMR exome

AF:

0.813

Gnomad ASJ exome

AF:

0.699

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.709

Gnomad FIN exome

AF:

0.815

Gnomad NFE exome

AF:

0.737

Gnomad OTH exome

AF:

0.750

GnomAD4 exome

AF:

0.747

AC:

1089034

AN:

1457848

Hom.:

408263

Cov.:

AF XY:

0.745

AC XY:

540488

AN XY:

725450

show subpopulations

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.810

Gnomad4 ASJ exome

AF:

0.702

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.814

Gnomad4 NFE exome

AF:

0.739

Gnomad4 OTH exome

AF:

0.742

GnomAD4 genome

AF:

0.783

AC:

119138

AN:

152116

Hom.:

46948

Cov.:

AF XY:

0.785

AC XY:

58352

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.860

Gnomad4 AMR

AF:

0.772

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.812

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.813

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.745

Alfa

AF:

0.744

Hom.:

83528

Bravo

AF:

0.783

Asia WGS

AF:

0.768

AC:

2673

AN:

3478

EpiCase

AF:

0.729

EpiControl

AF:

0.720

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 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

-0.59

CADD

Benign

0.38

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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