dbSNP rs11761888: CPA5:p.Leu336Ser (chr7-130367540-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080385.5(CPA5):c.1007T>C(p.Leu336Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,612,920 control chromosomes in the GnomAD database, including 37,055 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.24 ( 5198 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31857 hom. )

Consequence

CPA5
NM_080385.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

CPA5 (HGNC:15722): (carboxypeptidase A5) Carboxypeptidases have functions ranging from digestion of food to selective biosynthesis of neuroendocrine peptides. Members of the A/B subfamily of carboxypeptidases, such as CPA5, contain an approximately 90-amino acid pro region that assists in the folding of the active carboxypeptidase domain. Cleavage of the pro region activates the enzyme (Wei et al., 2002 [PubMed 11836249]).[supplied by OMIM, Mar 2008]

CPA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040917993).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA5	NM_080385.5 link	c.1007T>C	p.Leu336Ser	missense_variant	Exon 11 of 13	ENST00000474905.6	NP_525124.3	Q8WXQ8-1A4D1M2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA5	ENST00000474905.6 link	c.1007T>C	p.Leu336Ser	missense_variant	Exon 11 of 13	1	NM_080385.5	ENSP00000417314.1		Q8WXQ8-1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37057

AN:

151846

Hom.:

5184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.379

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.0256

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.213

Gnomad OTH

AF:

0.233

GnomAD3 exomes

AF:

0.186

AC:

46870

AN:

251464

Hom.:

5089

AF XY:

0.185

AC XY:

25150

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.107

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.0268

Gnomad SAS exome

AF:

0.135

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.217

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.202

AC:

295307

AN:

1460956

Hom.:

31857

Cov.:

AF XY:

0.200

AC XY:

145412

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.380

Gnomad4 AMR exome

AF:

0.112

Gnomad4 ASJ exome

AF:

0.204

Gnomad4 EAS exome

AF:

0.0230

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.206

GnomAD4 genome

AF:

0.244

AC:

37099

AN:

151964

Hom.:

5198

Cov.:

AF XY:

0.238

AC XY:

17660

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.0255

Gnomad4 SAS

AF:

0.136

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.213

Gnomad4 OTH

AF:

0.231

Alfa

AF:

0.211

Hom.:

7306

Bravo

AF:

0.247

TwinsUK

AF:

0.206

AC:

762

ALSPAC

AF:

0.210

AC:

811

ESP6500AA

AF:

0.379

AC:

1672

ESP6500EA

AF:

0.216

AC:

1854

ExAC

AF:

0.197

AC:

23871

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.0086

T;T;T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.014

.;.;.;T;.;T

MetaRNN

Benign

0.0041

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.4

N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

2.4

N;N;N;N;N;N

REVEL

Benign

0.080

Sift

Benign

0.41

T;T;T;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;B;B

Vest4

0.028

MPC

0.24

ClinPred

0.0049

GERP RS

3.7

Varity_R

0.033

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over