chr7-130367540-T-C

Variant names:

• chr7-130367540-T-C
• rs11761888
• NM_080385.5:c.1007T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 27 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080385.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA5	NM_080385.5	MANE Select	c.1007T>C	p.Leu336Ser	missense	Exon 11 of 13	NP_525124.3
	CPA5	NM_001127441.2		c.1007T>C	p.Leu336Ser	missense	Exon 12 of 14	NP_001120913.1
	CPA5	NM_001318223.2		c.1007T>C	p.Leu336Ser	missense	Exon 10 of 12	NP_001305152.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPA5	ENST00000474905.6	TSL:1 MANE Select	c.1007T>C	p.Leu336Ser	missense	Exon 11 of 13	ENSP00000417314.1
	CPA5	ENST00000393213.7	TSL:1	c.1007T>C	p.Leu336Ser	missense	Exon 9 of 11	ENSP00000376907.3
	CPA5	ENST00000461828.5	TSL:1	c.1007T>C	p.Leu336Ser	missense	Exon 10 of 12	ENSP00000418183.1

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

GnomAD2 exomes AF: 0.186 AC: 46870 AN: 251464 AF XY: 0.185

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 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

African (AFR) AF: 0.380 AC: 12709 AN: 33458

American (AMR) AF: 0.112 AC: 5030 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 5318 AN: 26124

East Asian (EAS) AF: 0.0230 AC: 914 AN: 39698

South Asian (SAS) AF: 0.136 AC: 11688 AN: 86248

European-Finnish (FIN) AF: 0.202 AC: 10812 AN: 53416

Middle Eastern (MID) AF: 0.257 AC: 1481 AN: 5758

European-Non Finnish (NFE) AF: 0.211 AC: 234935 AN: 1111166

Other (OTH) AF: 0.206 AC: 12420 AN: 60370

GnomAD4 genome AF: 0.244 AC: 37099 AN: 151964 Hom.: 5198 Cov.: 32 AF XY: 0.238 AC XY: 17660 AN XY: 74310

African (AFR) AF: 0.379 AC: 15684 AN: 41398

American (AMR) AF: 0.169 AC: 2584 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 711 AN: 3470

East Asian (EAS) AF: 0.0255 AC: 132 AN: 5174

South Asian (SAS) AF: 0.136 AC: 653 AN: 4810

European-Finnish (FIN) AF: 0.203 AC: 2152 AN: 10584

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.213 AC: 14504 AN: 67958

Other (OTH) AF: 0.231 AC: 487 AN: 2108

Alfa AF: 0.217 Hom.: 15396

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 v4.9

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
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.014	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.4	N
PhyloP100		1.2
PrimateAI	Benign	0.28	T
PROVEAN	Benign	2.4	N
REVEL	Benign	0.080
Sift	Benign	0.41	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.028
MPC		0.24
ClinPred		0.0049	T
GERP RS		3.7
Varity_R		0.033
gMVP		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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