chr19-44647342-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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

Publications

40 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PVR	NM_006505.5 link	c.199G>A	p.Ala67Thr	missense_variant	Exon 2 of 8	ENST00000425690.8	NP_006496.4	P15151A0A0C4DG49A8K4I1
PVR	NM_001135770.4 link	c.199G>A	p.Ala67Thr	missense_variant	Exon 2 of 6		NP_001129242.2	P15151A0A0A0MSA9
PVR	NM_001135768.3 link	c.199G>A	p.Ala67Thr	missense_variant	Exon 2 of 8		NP_001129240.1	P15151-2
PVR	NM_001135769.3 link	c.199G>A	p.Ala67Thr	missense_variant	Exon 2 of 7		NP_001129241.1	P15151-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8 link	c.199G>A	p.Ala67Thr	missense_variant	Exon 2 of 8	1	NM_006505.5	ENSP00000402060.2		A0A0C4DG49

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

GnomAD2 exomes

AF:

0.0774

AC:

19250

AN:

248850

AF XY:

0.0788

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 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

African (AFR)

AF:

0.0634

AC:

2121

AN:

33470

American (AMR)

AF:

0.107

AC:

4746

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.0840

AC:

2191

AN:

26096

East Asian (EAS)

AF:

0.157

AC:

6209

AN:

39642

South Asian (SAS)

AF:

0.164

AC:

14144

AN:

86022

European-Finnish (FIN)

AF:

0.0472

AC:

2515

AN:

53318

Middle Eastern (MID)

AF:

0.0623

AC:

359

AN:

5766

European-Non Finnish (NFE)

AF:

0.0453

AC:

50377

AN:

1111646

Other (OTH)

AF:

0.0612

AC:

3695

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

5059

10119

15178

20238

25297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2136

4272

6408

8544

10680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0580

AC:

8830

AN:

152256

Hom.:

331

Cov.:

AF XY:

0.0599

AC XY:

4459

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0630

AC:

2616

AN:

41550

American (AMR)

AF:

0.0653

AC:

999

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0767

AC:

266

AN:

3470

East Asian (EAS)

AF:

0.114

AC:

590

AN:

5166

South Asian (SAS)

AF:

0.157

AC:

757

AN:

4818

European-Finnish (FIN)

AF:

0.0457

AC:

485

AN:

10618

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0439

AC:

2984

AN:

68022

Other (OTH)

AF:

0.0482

AC:

102

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

414

827

1241

1654

2068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0510

Hom.:

1069

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

Aug 01, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

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;.

PhyloP100

-1.6

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over