Variant 3-148841864-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001871.3(CPB1):c.516C>A(p.Asp172Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,613,778 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0092 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 131 hom. )

Consequence

CPB1
NM_001871.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.190

Variant links:

Genes affected

CPB1 (HGNC:2299): (carboxypeptidase B1) Three different procarboxypeptidases A and two different procarboxypeptidases B have been isolated. The B1 and B2 forms differ from each other mainly in isoelectric point. Carboxypeptidase B1 is a highly tissue-specific protein and is a useful serum marker for acute pancreatitis and dysfunction of pancreatic transplants. It is not elevated in pancreatic carcinoma. [provided by RefSeq, Jul 2008]

CPB1 links:

CPB1 (HGNC:):

CPB1 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=0.01431182).

BP6

Variant 3-148841864-C-A is Benign according to our data. Variant chr3-148841864-C-A is described in ClinVar as [Benign]. Clinvar id is 3039545.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr3-148841864-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0122 (17807/1461486) while in subpopulation MID AF= 0.0321 (185/5768). AF 95% confidence interval is 0.0283. There are 131 homozygotes in gnomad4_exome. There are 8954 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPB1	NM_001871.3 linkuse as main transcript	c.516C>A	p.Asp172Glu	missense_variant	6/11	ENST00000282957.9	NP_001862.2	P15086

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPB1	ENST00000282957.9 linkuse as main transcript	c.516C>A	p.Asp172Glu	missense_variant	6/11	1	NM_001871.3	ENSP00000282957.4		P15086

Frequencies

GnomAD3 genomes

AF:

0.00921

AC:

1402

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.00832

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.0108

AC:

2713

AN:

251368

Hom.:

AF XY:

0.0113

AC XY:

1537

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00178

Gnomad AMR exome

AF:

0.00651

Gnomad ASJ exome

AF:

0.0312

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0117

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0129

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0122

AC:

17807

AN:

1461486

Hom.:

131

Cov.:

AF XY:

0.0123

AC XY:

8954

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00700

Gnomad4 ASJ exome

AF:

0.0310

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0132

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0152

GnomAD4 genome

AF:

0.00919

AC:

1399

AN:

152292

Hom.:

Cov.:

AF XY:

0.00907

AC XY:

675

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00831

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0128

Gnomad4 FIN

AF:

0.00773

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00971

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.0107

AC:

1304

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0160

EpiControl

AF:

0.0145

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CPB1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 27, 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

.;T;D

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.027

D;D;D

Sift4G

Benign

0.065

T;T;T

Polyphen

0.92

P;P;.

Vest4

0.29

MutPred

0.75

Loss of sheet (P = 0.302);Loss of sheet (P = 0.302);.;

MPC

0.74

ClinPred

0.043

GERP RS

1.4

Varity_R

0.82

gMVP

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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