19-44650098-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_006505.5(PVR):c.717C>T(p.Thr239=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,527,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

PVR
NM_006505.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.05

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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 19-44650098-C-T is Benign according to our data. Variant chr19-44650098-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 739035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PVR	NM_006505.5 linkuse as main transcript	c.717C>T	p.Thr239=	synonymous_variant	3/8	ENST00000425690.8
PVR	NM_001135770.4 linkuse as main transcript	c.717C>T	p.Thr239=	synonymous_variant	3/6
PVR	NM_001135768.3 linkuse as main transcript	c.717C>T	p.Thr239=	synonymous_variant	3/8
PVR	NM_001135769.3 linkuse as main transcript	c.717C>T	p.Thr239=	synonymous_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PVR	ENST00000425690.8 linkuse as main transcript	c.717C>T	p.Thr239=	synonymous_variant	3/8	1	NM_006505.5	P2
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.476-17479G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00413

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000558

AC:

103

AN:

184732

Hom.:

AF XY:

0.000430

AC XY:

AN XY:

97698

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.000631

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000692

Gnomad OTH exome

AF:

0.000937

GnomAD4 exome

AF:

0.000245

AC:

337

AN:

1375234

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

172

AN XY:

674234

show subpopulations

Gnomad4 AFR exome

AF:

0.00543

Gnomad4 AMR exome

AF:

0.000706

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000974

Gnomad4 OTH exome

AF:

0.000584

GnomAD4 genome

AF:

0.00125

AC:

191

AN:

152284

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00414

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.000515

Hom.:

Bravo

AF:

0.00150

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	PVR: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Mar 29, 2018	- -

PVR-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.71

Cadd

Benign

2.2

Dann

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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