dbSNP rs35385129: PVR:p.Arg391Ser (chr19-44658921-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001135770.4(PVR):c.1171C>A(p.Arg391Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,609,454 control chromosomes in the GnomAD database, including 21,972 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 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 0.14 ( 1757 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20215 hom. )

Consequence

PVR
NM_001135770.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.666

Variant links:

Genes affected

PVR (HGNC:9705): (PVR cell adhesion molecule) The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

PVR links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029010475).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5 link	c.1150+21C>A		intron_variant	Intron 6 of 7	ENST00000425690.8	NP_006496.4	P15151A0A0C4DG49A8K4I1
PVR	NM_001135770.4 link	c.1171C>A	p.Arg391Ser	missense_variant	Exon 6 of 6		NP_001129242.2	P15151A0A0A0MSA9
PVR	NM_001135768.3 link	c.1015+156C>A		intron_variant	Intron 6 of 7		NP_001129240.1	P15151-2
PVR	NM_001135769.3 link	c.991+1011C>A		intron_variant	Intron 5 of 6		NP_001129241.1	P15151-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8 link	c.1150+21C>A		intron_variant	Intron 6 of 7	1	NM_006505.5	ENSP00000402060.2		A0A0C4DG49

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21491

AN:

151970

Hom.:

1756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.343

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.156

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.163

AC:

40514

AN:

248384

Hom.:

4012

AF XY:

0.168

AC XY:

22563

AN XY:

134210

show subpopulations

Gnomad AFR exome

AF:

0.0805

Gnomad AMR exome

AF:

0.0668

Gnomad ASJ exome

AF:

0.163

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.213

Gnomad FIN exome

AF:

0.158

Gnomad NFE exome

AF:

0.160

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.160

AC:

233305

AN:

1457366

Hom.:

20215

Cov.:

AF XY:

0.162

AC XY:

117411

AN XY:

725040

show subpopulations

Gnomad4 AFR exome

AF:

0.0738

Gnomad4 AMR exome

AF:

0.0715

Gnomad4 ASJ exome

AF:

0.164

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.210

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.157

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.141

AC:

21490

AN:

152088

Hom.:

1757

Cov.:

AF XY:

0.142

AC XY:

10584

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0812

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.156

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.157

Hom.:

3023

Bravo

AF:

0.132

TwinsUK

AF:

0.160

AC:

595

ALSPAC

AF:

0.166

AC:

641

ESP6500AA

AF:

0.0833

AC:

367

ESP6500EA

AF:

0.161

AC:

1382

ExAC

AF:

0.166

AC:

20165

Asia WGS

AF:

0.249

AC:

866

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

2.5

DANN

Benign

0.71

DEOGEN2

Benign

0.0099

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

PROVEAN

Benign

0.96

REVEL

Benign

0.046

Sift

Benign

0.14

Sift4G

Benign

0.60

Vest4

0.098

ClinPred

0.000040

GERP RS

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over