rs968404

Positions:

chr7-130382200-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001868.4(CPA1):c.474C>T(p.Tyr158=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,612,924 control chromosomes in the GnomAD database, including 16,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1432 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15511 hom. )

Consequence

CPA1
NM_001868.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.46

Variant links:

Genes affected

CPA1 (HGNC:2296): (carboxypeptidase A1) This gene encodes a member of the carboxypeptidase A family of zinc metalloproteases. This enzyme is produced in the pancreas and preferentially cleaves C-terminal branched-chain and aromatic amino acids from dietary proteins. This gene and several family members are present in a gene cluster on chromosome 7. Mutations in this gene may be linked to chronic pancreatitis, while elevated protein levels may be associated with pancreatic cancer. [provided by RefSeq, Jan 2015]

CPA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-130382200-C-T is Benign according to our data. Variant chr7-130382200-C-T is described in ClinVar as [Benign]. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPA1	NM_001868.4 linkuse as main transcript	c.474C>T	p.Tyr158=	synonymous_variant	4/10	ENST00000011292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA1	ENST00000011292.8 linkuse as main transcript	c.474C>T	p.Tyr158=	synonymous_variant	4/10	1	NM_001868.4	P1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20284

AN:

152142

Hom.:

1432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.127

AC:

31795

AN:

251280

Hom.:

2299

AF XY:

0.131

AC XY:

17724

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.124

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.142

AC:

207005

AN:

1460664

Hom.:

15511

Cov.:

AF XY:

0.142

AC XY:

103030

AN XY:

726670

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0699

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.139

GnomAD4 genome

AF:

0.133

AC:

20290

AN:

152260

Hom.:

1432

Cov.:

AF XY:

0.133

AC XY:

9873

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.124

Gnomad4 AMR

AF:

0.100

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.00327

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.145

Hom.:

3717

Bravo

AF:

0.127

Asia WGS

AF:

0.0610

AC:

214

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hereditary pancreatitis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2018

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

DANN

Benign

0.35

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