chr19-44647342-G-A

Position:

chr19-44647342-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_006505.5(PVR):c.199G>A(p.Ala67Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 1,613,098 control chromosomes in the GnomAD database, including 4,055 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.058 ( 331 hom., cov: 30)

Exomes 𝑓: 0.059 ( 3724 hom. )

Consequence

PVR
NM_006505.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013558567).

BP6

Variant 19-44647342-G-A is Benign according to our data. Variant chr19-44647342-G-A is described in ClinVar as [Benign]. Clinvar id is 3056684.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PVR	NM_006505.5 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	2/8	ENST00000425690.8
PVR	NM_001135770.4 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	2/6
PVR	NM_001135768.3 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	2/8
PVR	NM_001135769.3 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVR	ENST00000425690.8 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	2/8	1	NM_006505.5	P2
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.476-14723C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0580

AC:

8821

AN:

152138

Hom.:

331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0648

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.158

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0439

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0774

AC:

19250

AN:

248850

Hom.:

1056

AF XY:

0.0788

AC XY:

10607

AN XY:

134626

show subpopulations

Gnomad AFR exome

AF:

0.0613

Gnomad AMR exome

AF:

0.110

Gnomad ASJ exome

AF:

0.0836

Gnomad EAS exome

AF:

0.114

Gnomad SAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0478

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0618

GnomAD4 exome

AF:

0.0591

AC:

86357

AN:

1460842

Hom.:

3724

Cov.:

AF XY:

0.0620

AC XY:

45049

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.0840

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.0472

Gnomad4 NFE exome

AF:

0.0453

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0580

AC:

8830

AN:

152256

Hom.:

331

Cov.:

AF XY:

0.0599

AC XY:

4459

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0630

Gnomad4 AMR

AF:

0.0653

Gnomad4 ASJ

AF:

0.0767

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.157

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.0439

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0508

Hom.:

562

Bravo

AF:

0.0589

TwinsUK

AF:

0.0456

AC:

169

ALSPAC

AF:

0.0545

AC:

210

ESP6500AA

AF:

0.0620

AC:

273

ESP6500EA

AF:

0.0486

AC:

418

ExAC

AF:

0.0770

AC:

9344

Asia WGS

AF:

0.137

AC:

475

AN:

3478

EpiCase

AF:

0.0426

EpiControl

AF:

0.0418

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PVR-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 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

0.064

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.023

DANN

Benign

0.70

DEOGEN2

Benign

0.0053

T;.;.;T

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.44

T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

.;N;N;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.48

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.76

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.013

MPC

0.34

ClinPred

0.0042

GERP RS

-9.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over