Variant rs1059502 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001871.3(CPB1):c.622G>A(p.Asp208Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,612,786 control chromosomes in the GnomAD database, including 44,685 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 0.24 ( 4630 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40055 hom. )

Consequence

CPB1
NM_001871.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.624

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.2314997E-4).

BP6

Variant 3-148844523-G-A is Benign according to our data. Variant chr3-148844523-G-A is described in ClinVar as [Benign]. Clinvar id is 3059113.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPB1	NM_001871.3 linkuse as main transcript	c.622G>A	p.Asp208Asn	missense_variant	7/11	ENST00000282957.9	NP_001862.2	P15086

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CPB1	ENST00000282957.9 linkuse as main transcript	c.622G>A	p.Asp208Asn	missense_variant	7/11	1	NM_001871.3	ENSP00000282957.4	P15086
CPB1	ENST00000491148.5 linkuse as main transcript	c.622G>A	p.Asp208Asn	missense_variant	8/12	5		ENSP00000417222.1	P15086
CPB1	ENST00000468341.1 linkuse as main transcript	c.520G>A	p.Asp174Asn	missense_variant	6/7	3		ENSP00000419427.1	C9JUX7
CPB1	ENST00000484877.1 linkuse as main transcript	n.*27G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37011

AN:

151944

Hom.:

4624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.214

GnomAD3 exomes

AF:

0.224

AC:

56168

AN:

250960

Hom.:

6710

AF XY:

0.226

AC XY:

30641

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.218

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.231

AC:

337317

AN:

1460724

Hom.:

40055

Cov.:

AF XY:

0.232

AC XY:

168553

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.240

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.244

AC:

37036

AN:

152062

Hom.:

4630

Cov.:

AF XY:

0.242

AC XY:

17955

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.176

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.285

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.215

Alfa

AF:

0.219

Hom.:

9024

Bravo

AF:

0.239

TwinsUK

AF:

0.239

AC:

888

ALSPAC

AF:

0.226

AC:

871

ESP6500AA

AF:

0.308

AC:

1358

ESP6500EA

AF:

0.206

AC:

1769

ExAC

AF:

0.229

AC:

27749

Asia WGS

AF:

0.292

AC:

1016

AN:

3478

EpiCase

AF:

0.208

EpiControl

AF:

0.205

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

Oct 21, 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

0.10

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.24

DANN

Benign

0.27

DEOGEN2

Benign

0.037

T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.078

LIST_S2

Benign

0.45

.;T;T

MetaRNN

Benign

0.00052

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.67

N;N;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.97

N;N;N

REVEL

Benign

0.013

Sift

Benign

0.88

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.045

MPC

0.20

ClinPred

0.00085

GERP RS

-2.8

Varity_R

0.047

gMVP

0.75

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