chr7-29030704-C-T

Variant names:

• chr7-29030704-C-T
• rs1052200
• NM_031311.5:c.1193G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031311.5(CPVL):​c.1193G>A​(p.Arg398His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,612,912 control chromosomes in the GnomAD database, including 23,012 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.17 (2518 hom., cov: 32)
  • Exomes 𝑓: 0.16 (20494 hom.)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 30 publications found

Genes affected

CPVL (HGNC:14399): (carboxypeptidase vitellogenic like) The protein encoded by this gene is a carboxypeptidase and bears strong sequence similarity to serine carboxypeptidases. Carboxypeptidases are a large class of proteases that act to cleave a single amino acid from the carboxy termini of proteins or peptides. The exact function of this protein, however, has not been determined. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018001497).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPVL	NM_031311.5	c.1193G>A	p.Arg398His	missense_variant	Exon 12 of 13	ENST00000265394.10	NP_112601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000265394.10	c.1193G>A	p.Arg398His	missense_variant	Exon 12 of 13	1	NM_031311.5	ENSP00000265394.5

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26245 AN: 151878 Hom.: 2513 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.157

GnomAD2 exomes AF: 0.192 AC: 47964 AN: 250310 AF XY: 0.187

Gnomad AFR exome AF: 0.162

Gnomad AMR exome AF: 0.290

Gnomad ASJ exome AF: 0.171

Gnomad EAS exome AF: 0.270

Gnomad FIN exome AF: 0.237

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.174

GnomAD4 exome AF: 0.160 AC: 234213 AN: 1460916 Hom.: 20494 Cov.: 35 AF XY: 0.161 AC XY: 116739 AN XY: 726734

African (AFR) AF: 0.168 AC: 5613 AN: 33428

American (AMR) AF: 0.286 AC: 12777 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 4514 AN: 26100

East Asian (EAS) AF: 0.305 AC: 12065 AN: 39614

South Asian (SAS) AF: 0.192 AC: 16503 AN: 86078

European-Finnish (FIN) AF: 0.240 AC: 12809 AN: 53394

Middle Eastern (MID) AF: 0.158 AC: 909 AN: 5762

European-Non Finnish (NFE) AF: 0.143 AC: 159219 AN: 1111520

Other (OTH) AF: 0.162 AC: 9804 AN: 60370

GnomAD4 genome AF: 0.173 AC: 26285 AN: 151996 Hom.: 2518 Cov.: 32 AF XY: 0.179 AC XY: 13273 AN XY: 74290

African (AFR) AF: 0.163 AC: 6755 AN: 41448

American (AMR) AF: 0.226 AC: 3447 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1420 AN: 5152

South Asian (SAS) AF: 0.195 AC: 938 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2629 AN: 10558

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.147 AC: 9989 AN: 67970

Other (OTH) AF: 0.161 AC: 340 AN: 2114

Alfa AF: 0.154 Hom.: 8758

Bravo AF: 0.169

TwinsUK AF: 0.141 AC: 521

ALSPAC AF: 0.137 AC: 528

ESP6500AA AF: 0.158 AC: 695

ESP6500EA AF: 0.143 AC: 1227

ExAC AF: 0.188 AC: 22804

Asia WGS AF: 0.243 AC: 843 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.37	T;T;.;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.70	.;.;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M;.;M
PhyloP100		1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.95	N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.11	T;T;T;T
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.51	P;P;.;P
Vest4		0.062
MPC		0.38
ClinPred		0.011	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1052200; hg19: chr7-29070320; COSMIC: COSV55300005;