rs11761888

chr7-130367540-T-Cchr7-130367540-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (5198 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31857 hom.)
• Consequence: CPA5 NM_080385.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ACMG classification

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/exons	MANE	UniProt
CPA5	NM_080385.5	c.1007T>C	p.Leu336Ser	missense_variant	11/13	ENST00000474905.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPA5	ENST00000474905.6	c.1007T>C	p.Leu336Ser	missense_variant	11/13	1	NM_080385.5	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37057 AN: 151846 Hom.: 5184 Cov.: 32

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

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.: 34 AF XY: 0.200 AC XY: 145412 AN XY: 726828

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.: 32 AF XY: 0.238 AC XY: 17660 AN XY: 74310

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	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	12
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	N
MetaRNN	Benign	0.0041	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.4	N;N;N;N;N;N
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs11761888; hg19: chr7-130007381; COSMIC: COSV62570438;