rs35385129

chr19-44658921-C-Achr19-44658921-C-T

Variant summary

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

The ENST00000406449.8(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 ENST00000406449.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666

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]

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

ACMG classification

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/exons	MANE	UniProt
PVR	NM_006505.5	c.1150+21C>A		intron_variant		ENST00000425690.8
PVR	NM_001135770.4	c.1171C>A	p.Arg391Ser	missense_variant	6/6
PVR	NM_001135768.3	c.1015+156C>A		intron_variant
PVR	NM_001135769.3	c.991+1011C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVR	ENST00000425690.8	c.1150+21C>A		intron_variant		1	NM_006505.5	P2
CEACAM16-AS1	ENST00000662585.1	n.476-26302G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21491 AN: 151970 Hom.: 1756 Cov.: 32

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

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.: 31 AF XY: 0.162 AC XY: 117411 AN XY: 725040

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.: 32 AF XY: 0.142 AC XY: 10584 AN XY: 74324

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	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	2.5
Dann	Benign	0.71
DEOGEN2	Benign	0.0099	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	0.96	N
REVEL	Benign	0.046
Sift	Benign	0.14	T
Sift4G	Benign	0.60	T
Vest4		0.098
ClinPred		0.000040	T
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

Other links and lift over

dbSNP: rs35385129; hg19: chr19-45162189; COSMIC: COSV51822053; COSMIC: COSV51822053;