19-44657802-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006505.5(PVR):c.883G>A(p.Ala295Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,613,912 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.045 (542 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (503 hom.)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.85

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0022646189).
• BP6: Variant 19-44657802-G-A is Benign according to our data. Variant chr19-44657802-G-A is described in ClinVar as [Benign]. Clinvar id is 3038393.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PVR	NM_006505.5	c.883G>A	p.Ala295Thr	missense_variant	5/8	ENST00000425690.8
PVR	NM_001135770.4	c.883G>A	p.Ala295Thr	missense_variant	5/6
PVR	NM_001135768.3	c.883G>A	p.Ala295Thr	missense_variant	5/8
PVR	NM_001135769.3	c.883G>A	p.Ala295Thr	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVR	ENST00000425690.8	c.883G>A	p.Ala295Thr	missense_variant	5/8	1	NM_006505.5	P2
CEACAM16-AS1	ENST00000662585.1	n.476-25183C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0444 AC: 6761 AN: 152106 Hom.: 536 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0134 AC: 3357 AN: 251054 Hom.: 210 AF XY: 0.0107 AC XY: 1459 AN XY: 135742

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.00921

Gnomad ASJ exome AF: 0.00338

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0112

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000951

Gnomad OTH exome AF: 0.00702

GnomAD4 exome AF: 0.00560 AC: 8187 AN: 1461688 Hom.: 503 Cov.: 31 AF XY: 0.00532 AC XY: 3867 AN XY: 727168

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.00306

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0110

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000582

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.0446 AC: 6794 AN: 152224 Hom.: 542 Cov.: 33 AF XY: 0.0443 AC XY: 3294 AN XY: 74416

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000941

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.00816 Hom.: 133

Bravo AF: 0.0501

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.149 AC: 656

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.0164 AC: 1986

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PVR-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.071
Dann	Benign	0.78
DEOGEN2	Benign	0.0048	T;.;.;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.14	T;T;T;T
MetaRNN	Benign	0.0023	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.12	N;N;N;N
REVEL	Benign	0.0090
Sift	Benign	0.41	T;T;T;T
Sift4G	Benign	0.50	T;T;T;T
Polyphen		0.15, 0.038	.;B;B;.
Vest4		0.016
MPC		0.43
ClinPred		0.0015	T
GERP RS		-10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs35365841; hg19: chr19-45161070;