7-130381647-G-C

Variant names:

• chr7-130381647-G-C
• rs1126899
• NM_001868.4:c.165G>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23469 hom., cov: 32)
  • Exomes 𝑓: 0.52 (197873 hom.)
• Consequence: CPA1 NM_001868.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.02

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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	c.165G>C	p.Gly55Gly	synonymous_variant	Exon 3 of 10	ENST00000011292.8	NP_001859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA1	ENST00000011292.8	c.165G>C	p.Gly55Gly	synonymous_variant	Exon 3 of 10	1	NM_001868.4	ENSP00000011292.3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83821 AN: 151838 Hom.: 23454 Cov.: 32

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

GnomAD3 exomes AF: 0.536 AC: 133603 AN: 249372 Hom.: 36106 AF XY: 0.528 AC XY: 71310 AN XY: 135096

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 SAS exome AF: 0.489

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.: 46 AF XY: 0.517 AC XY: 375687 AN XY: 726828

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.552

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.491

Gnomad4 FIN exome AF: 0.531

Gnomad4 NFE exome AF: 0.508

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.552 AC: 83886 AN: 151956 Hom.: 23469 Cov.: 32 AF XY: 0.551 AC XY: 40894 AN XY: 74240

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.529

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

Submissions by phenotype

not provided Benign:3

Nov 10, 2018

GeneDx

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

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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
DANN	Benign	0.66

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

Other links and lift over

dbSNP: rs1126899; hg19: chr7-130021488; COSMIC: COSV50568158; COSMIC: COSV50568158;