19-44647519-G-A

Variant names:

• chr19-44647519-G-A
• rs138482699
• NM_006505.5:c.376G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006505.5(PVR):​c.376G>A​(p.Val126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,614,036 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40
• Publications: 3 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059283376).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006505.5. 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
	PVR	NM_006505.5	MANE Select	c.376G>A	p.Val126Ile	missense	Exon 2 of 8	NP_006496.4
	PVR	NM_001135770.4		c.376G>A	p.Val126Ile	missense	Exon 2 of 6	NP_001129242.2	A0A0A0MSA9
	PVR	NM_001135768.3		c.376G>A	p.Val126Ile	missense	Exon 2 of 8	NP_001129240.1	P15151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	ENST00000425690.8	TSL:1 MANE Select	c.376G>A	p.Val126Ile	missense	Exon 2 of 8	ENSP00000402060.2	A0A0C4DG49
	PVR	ENST00000406449.8	TSL:1	c.376G>A	p.Val126Ile	missense	Exon 2 of 6	ENSP00000383907.3	A0A0A0MSA9
	PVR	ENST00000971445.1		c.376G>A	p.Val126Ile	missense	Exon 2 of 8	ENSP00000641504.1

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152130 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000225 AC: 56 AN: 248590 AF XY: 0.000319

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 334 AN: 1461788 Hom.: 1 Cov.: 32 AF XY: 0.000265 AC XY: 193 AN XY: 727196

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00121 AC: 104 AN: 86244

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53404

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000183 AC: 203 AN: 1111960

Other (OTH) AF: 0.000215 AC: 13 AN: 60386

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152248 Hom.: 0 Cov.: 30 AF XY: 0.000215 AC XY: 16 AN XY: 74440

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.000392 AC: 6 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000119 Hom.: 0

Bravo AF: 0.000170

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.059	T
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.86	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.048	D
Polyphen		0.23	B
Vest4		0.056
MVP		0.63
MPC		0.45
ClinPred		0.043	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.29
Mutation Taster		=89/11	polymorphism

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: rs138482699; hg19: chr19-45150791;