7-130383698-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001868.4(CPA1):c.600C>T(p.Tyr200Tyr) 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:5

Conservation

PhyloP100: -0.198

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

hereditary chronic pancreatitis
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

CPA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPA1	NM_001868.4 link	c.600C>T	p.Tyr200Tyr	synonymous_variant	Exon 6 of 10	ENST00000011292.8	NP_001859.1	P15085

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA1	ENST00000011292.8 link	c.600C>T	p.Tyr200Tyr	synonymous_variant	Exon 6 of 10	1	NM_001868.4	ENSP00000011292.3		P15085

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

GnomAD2 exomes

AF:

0.0991

AC:

24906

AN:

251294

AF XY:

0.103

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 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

African (AFR)

AF:

0.0891

AC:

2980

AN:

33456

American (AMR)

AF:

0.0556

AC:

2485

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

2742

AN:

26126

East Asian (EAS)

AF:

0.00118

AC:

AN:

39700

South Asian (SAS)

AF:

0.103

AC:

8843

AN:

86206

European-Finnish (FIN)

AF:

0.115

AC:

6153

AN:

53400

Middle Eastern (MID)

AF:

0.155

AC:

892

AN:

5760

European-Non Finnish (NFE)

AF:

0.116

AC:

129096

AN:

1110602

Other (OTH)

AF:

0.103

AC:

6189

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6864

13727

20591

27454

34318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4488

8976

13464

17952

22440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.104

AC:

15764

AN:

152254

Hom.:

876

Cov.:

AF XY:

0.102

AC XY:

7619

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0938

AC:

3899

AN:

41550

American (AMR)

AF:

0.0830

AC:

1270

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

338

AN:

3470

East Asian (EAS)

AF:

0.00290

AC:

AN:

5176

South Asian (SAS)

AF:

0.104

AC:

503

AN:

4826

European-Finnish (FIN)

AF:

0.125

AC:

1324

AN:

10610

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8102

AN:

68004

Other (OTH)

AF:

0.114

AC:

240

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

741

1482

2224

2965

3706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

1714

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary pancreatitis

Benign:1

Sep 14, 2018

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.27

PhyloP100

-0.20

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over