rs7313

Variant names:

• chr7-29030593-G-A
• rs7313
• NM_031311.5:c.1304C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-29030593-G-A
• chr7-29030593-G-T

Variant summary

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

The NM_001371264.1(CPVL):​c.1346C>T​(p.Ala449Val) 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. 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 0.38 (11917 hom., cov: 32)
  • Exomes 𝑓: 0.45 (149136 hom.)
• Consequence: CPVL NM_001371264.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 37 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=0.0019314289).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371264.1. 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
	CPVL	NM_031311.5	MANE Select	c.1304C>T	p.Ala435Val	missense	Exon 12 of 13	NP_112601.3
	CPVL	NM_001371264.1		c.1346C>T	p.Ala449Val	missense	Exon 15 of 16	NP_001358193.1
	CPVL	NM_001348052.1		c.1304C>T	p.Ala435Val	missense	Exon 14 of 15	NP_001334981.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPVL	ENST00000265394.10	TSL:1 MANE Select	c.1304C>T	p.Ala435Val	missense	Exon 12 of 13	ENSP00000265394.5
	CPVL	ENST00000396276.7	TSL:1	c.1304C>T	p.Ala435Val	missense	Exon 12 of 13	ENSP00000379572.3
	CPVL	ENST00000409850.5	TSL:2	c.1304C>T	p.Ala435Val	missense	Exon 16 of 17	ENSP00000387164.1

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

GnomAD2 exomes AF: 0.390 AC: 97120 AN: 248748 AF XY: 0.399

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 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

African (AFR) AF: 0.262 AC: 8735 AN: 33370

American (AMR) AF: 0.331 AC: 14714 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 10901 AN: 26002

East Asian (EAS) AF: 0.163 AC: 6433 AN: 39558

South Asian (SAS) AF: 0.389 AC: 33293 AN: 85678

European-Finnish (FIN) AF: 0.398 AC: 21238 AN: 53312

Middle Eastern (MID) AF: 0.410 AC: 2362 AN: 5760

European-Non Finnish (NFE) AF: 0.475 AC: 527627 AN: 1110582

Other (OTH) AF: 0.428 AC: 25811 AN: 60306

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

African (AFR) AF: 0.272 AC: 11283 AN: 41442

American (AMR) AF: 0.358 AC: 5469 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1461 AN: 3468

East Asian (EAS) AF: 0.135 AC: 697 AN: 5166

South Asian (SAS) AF: 0.381 AC: 1832 AN: 4808

European-Finnish (FIN) AF: 0.392 AC: 4134 AN: 10556

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32099 AN: 67962

Other (OTH) AF: 0.386 AC: 816 AN: 2114

Alfa AF: 0.435 Hom.: 57980

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 v4.9

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
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.86	N
PhyloP100		2.2
PrimateAI	Benign	0.32	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.071
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0040	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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7313; hg19: chr7-29070209; COSMIC: COSV55302996;