chr7-29030593-G-A

Position:

• chr7-29030593-G-A

Variant summary

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

The NM_031311.5(CPVL):​c.1304C>T​(p.Ala435Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,611,010 control chromosomes in the GnomAD database, including 161,053 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 0.38 (11917 hom., cov: 32)
  • Exomes 𝑓: 0.45 (149136 hom.)
• Consequence: CPVL NM_031311.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019314289).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPVL	NM_031311.5	c.1304C>T	p.Ala435Val	missense_variant	12/13	ENST00000265394.10	NP_112601.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPVL	ENST00000265394.10	c.1304C>T	p.Ala435Val	missense_variant	12/13	1	NM_031311.5	ENSP00000265394.5

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58149 AN: 151860 Hom.: 11914 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.390 AC: 97120 AN: 248748 Hom.: 20089 AF XY: 0.399 AC XY: 53658 AN XY: 134452

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.383

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.466

Gnomad OTH exome AF: 0.407

GnomAD4 exome AF: 0.446 AC: 651114 AN: 1459032 Hom.: 149136 Cov.: 42 AF XY: 0.446 AC XY: 323357 AN XY: 725710

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.383 AC: 58176 AN: 151978 Hom.: 11917 Cov.: 32 AF XY: 0.376 AC XY: 27963 AN XY: 74296

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.358

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.386

Alfa AF: 0.445 Hom.: 40092

Bravo AF: 0.374

TwinsUK AF: 0.476 AC: 1764

ALSPAC AF: 0.474 AC: 1825

ESP6500AA AF: 0.281 AC: 1240

ESP6500EA AF: 0.464 AC: 3994

ExAC AF: 0.390 AC: 47398

Asia WGS AF: 0.240 AC: 839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Benign	0.31
DEOGEN2	Benign	0.16	T;T;.;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.28	.;.;T;T
MetaRNN	Benign	0.0019	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.86	N;N;.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.2	N;N;N;N
REVEL	Benign	0.071
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0040	B;B;.;B
Vest4		0.12
MPC		0.22
ClinPred		0.0074	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7313; hg19: chr7-29070209; COSMIC: COSV55302996;