NM_001868.4:c.165G>C

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.165G>C(p.Gly55Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,612,906 control chromosomes in the GnomAD database, including 221,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G55G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.55 ( 23469 hom., cov: 32)

Exomes 𝑓: 0.52 ( 197873 hom. )

Consequence

CPA1
NM_001868.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.02

Publications

21 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=-0.82).

BP6

Variant 7-130381647-G-C is Benign according to our data. Variant chr7-130381647-G-C is described in ClinVar as Benign. ClinVar VariationId is 258474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA1	NM_001868.4 link	c.165G>C	p.Gly55Gly	synonymous_variant	Exon 3 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.165G>C	p.Gly55Gly	synonymous_variant	Exon 3 of 10	1	NM_001868.4	ENSP00000011292.3		P15085

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83821

AN:

151838

Hom.:

23454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.644

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.604

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.526

GnomAD2 exomes

AF:

0.536

AC:

133603

AN:

249372

AF XY:

0.528

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.591

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.587

Gnomad FIN exome

AF:

0.528

Gnomad NFE exome

AF:

0.506

Gnomad OTH exome

AF:

0.533

GnomAD4 exome

AF:

0.518

AC:

757217

AN:

1460950

Hom.:

197873

Cov.:

AF XY:

0.517

AC XY:

375687

AN XY:

726828

show subpopulations

African (AFR)

AF:

0.656

AC:

21956

AN:

33456

American (AMR)

AF:

0.586

AC:

26223

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

14415

AN:

26118

East Asian (EAS)

AF:

0.614

AC:

24368

AN:

39694

South Asian (SAS)

AF:

0.491

AC:

42357

AN:

86232

European-Finnish (FIN)

AF:

0.531

AC:

28240

AN:

53144

Middle Eastern (MID)

AF:

0.518

AC:

2987

AN:

5766

European-Non Finnish (NFE)

AF:

0.508

AC:

564923

AN:

1111460

Other (OTH)

AF:

0.526

AC:

31748

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

19320

38640

57961

77281

96601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16520

33040

49560

66080

82600

<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:

0.552

AC:

83886

AN:

151956

Hom.:

23469

Cov.:

AF XY:

0.551

AC XY:

40894

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.644

AC:

26709

AN:

41456

American (AMR)

AF:

0.545

AC:

8324

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1951

AN:

3468

East Asian (EAS)

AF:

0.604

AC:

3101

AN:

5138

South Asian (SAS)

AF:

0.492

AC:

2371

AN:

4818

European-Finnish (FIN)

AF:

0.523

AC:

5516

AN:

10552

Middle Eastern (MID)

AF:

0.500

AC:

146

AN:

292

European-Non Finnish (NFE)

AF:

0.502

AC:

34091

AN:

67926

Other (OTH)

AF:

0.529

AC:

1118

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1927

3854

5781

7708

9635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.482

Hom.:

4977

Bravo

AF:

0.559

Asia WGS

AF:

0.553

AC:

1920

AN:

3478

EpiCase

AF:

0.493

EpiControl

AF:

0.506

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 12, 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

-0.82

CADD

Benign

6.5

(source)

DANN

Benign

0.66

PhyloP100

-1.0

Mutation Taster

=300/0

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