7-130382200-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.474C>T(p.Tyr158Tyr) 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:5

Conservation

PhyloP100: -1.46

Publications

13 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=-0.8).

BP6

Variant 7-130382200-C-T is Benign according to our data. Variant chr7-130382200-C-T is described in CliVar as Benign. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130382200-C-T is described in CliVar as Benign. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130382200-C-T is described in CliVar as Benign. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130382200-C-T is described in CliVar as Benign. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130382200-C-T is described in CliVar as Benign. Clinvar id is 258475.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130382200-C-T is described in CliVar 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 rank	MANE	Protein	UniProt
CPA1	NM_001868.4 link	c.474C>T	p.Tyr158Tyr	synonymous_variant	Exon 4 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.474C>T	p.Tyr158Tyr	synonymous_variant	Exon 4 of 10	1	NM_001868.4	ENSP00000011292.3		P15085

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

GnomAD2 exomes

AF:

0.127

AC:

31795

AN:

251280

AF XY:

0.131

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 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

African (AFR)

AF:

0.117

AC:

3920

AN:

33462

American (AMR)

AF:

0.0699

AC:

3126

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3957

AN:

26124

East Asian (EAS)

AF:

0.00144

AC:

AN:

39700

South Asian (SAS)

AF:

0.124

AC:

10723

AN:

86234

European-Finnish (FIN)

AF:

0.160

AC:

8541

AN:

53368

Middle Eastern (MID)

AF:

0.195

AC:

1123

AN:

5762

European-Non Finnish (NFE)

AF:

0.150

AC:

167194

AN:

1110926

Other (OTH)

AF:

0.139

AC:

8364

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8480

16959

25439

33918

42398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5802

11604

17406

23208

29010

<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:

0.133

AC:

20290

AN:

152260

Hom.:

1432

Cov.:

AF XY:

0.133

AC XY:

9873

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.124

AC:

5150

AN:

41538

American (AMR)

AF:

0.100

AC:

1534

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

510

AN:

3470

East Asian (EAS)

AF:

0.00327

AC:

AN:

5194

South Asian (SAS)

AF:

0.121

AC:

585

AN:

4824

European-Finnish (FIN)

AF:

0.171

AC:

1817

AN:

10608

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.151

AC:

10283

AN:

68010

Other (OTH)

AF:

0.140

AC:

295

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

934

1867

2801

3734

4668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

232

464

696

928

1160

<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:

0.144

Hom.:

6956

Bravo

AF:

0.127

Asia WGS

AF:

0.0610

AC:

214

AN:

3478

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

- -

Nov 10, 2018

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

-0.80

CADD

Benign

3.3

(source)

DANN

Benign

0.35

PhyloP100

-1.5

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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