Variant 7-130383698-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001868.4(CPA1):c.600C>T(p.Tyr200=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,612,562 control chromosomes in the GnomAD database, including 10,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 876 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9291 hom. )

Consequence

CPA1
NM_001868.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.198

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 7-130383698-C-T is Benign according to our data. Variant chr7-130383698-C-T is described in ClinVar as [Benign]. Clinvar id is 258476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.198 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 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.600C>T	p.Tyr200=	synonymous_variant	6/10	ENST00000011292.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA1	ENST00000011292.8 linkuse as main transcript	c.600C>T	p.Tyr200=	synonymous_variant	6/10	1	NM_001868.4	P1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15766

AN:

152136

Hom.:

877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0939

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0833

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.00289

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.125

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0991

AC:

24906

AN:

251294

Hom.:

1399

AF XY:

0.103

AC XY:

13997

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0955

Gnomad AMR exome

AF:

0.0541

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.00179

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.124

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.109

AC:

159427

AN:

1460308

Hom.:

9291

Cov.:

AF XY:

0.109

AC XY:

79537

AN XY:

726566

show subpopulations

Gnomad4 AFR exome

AF:

0.0891

Gnomad4 AMR exome

AF:

0.0556

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.00118

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.104

AC:

15764

AN:

152254

Hom.:

876

Cov.:

AF XY:

0.102

AC XY:

7619

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0938

Gnomad4 AMR

AF:

0.0830

Gnomad4 ASJ

AF:

0.0974

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.125

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.110

Hom.:

1360

Bravo

AF:

0.0990

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.121

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	Jun 14, 2019	- -

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

-0.54

Cadd

Benign

3.3

Dann

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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