chr19-44650057-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_006505.5(PVR):c.676G>A(p.Glu226Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,554,248 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 16 hom. )

Consequence

PVR
NM_006505.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.37

Publications

8 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=0.008191377).

BP6

Variant 19-44650057-G-A is Benign according to our data. Variant chr19-44650057-G-A is described in ClinVar as [Benign]. Clinvar id is 3034003.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0012 (183/152308) while in subpopulation EAS AF = 0.0276 (143/5190). AF 95% confidence interval is 0.0239. There are 2 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5 link	c.676G>A	p.Glu226Lys	missense_variant	Exon 3 of 8	ENST00000425690.8	NP_006496.4	P15151A0A0C4DG49A8K4I1
PVR	NM_001135770.4 link	c.676G>A	p.Glu226Lys	missense_variant	Exon 3 of 6		NP_001129242.2	P15151A0A0A0MSA9
PVR	NM_001135768.3 link	c.676G>A	p.Glu226Lys	missense_variant	Exon 3 of 8		NP_001129240.1	P15151-2
PVR	NM_001135769.3 link	c.676G>A	p.Glu226Lys	missense_variant	Exon 3 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.676G>A	p.Glu226Lys	missense_variant	Exon 3 of 8	1	NM_006505.5	ENSP00000402060.2		A0A0C4DG49

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0275

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00285

AC:

571

AN:

200178

AF XY:

0.00250

show subpopulations

Gnomad AFR exome

AF:

0.000446

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0316

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000432

Gnomad OTH exome

AF:

0.00193

GnomAD4 exome

AF:

0.000739

AC:

1036

AN:

1401940

Hom.:

Cov.:

AF XY:

0.000730

AC XY:

504

AN XY:

690746

show subpopulations

African (AFR)

AF:

0.000189

AC:

AN:

31786

American (AMR)

AF:

0.00

AC:

AN:

36792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21752

East Asian (EAS)

AF:

0.0188

AC:

736

AN:

39160

South Asian (SAS)

AF:

0.00115

AC:

AN:

76762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.0000721

AC:

AN:

1081522

Other (OTH)

AF:

0.00222

AC:

128

AN:

57736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

116

174

232

290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00120

AC:

183

AN:

152308

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

109

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41574

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.0276

AC:

143

AN:

5190

South Asian (SAS)

AF:

0.00187

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00124

Hom.:

Bravo

AF:

0.00144

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00224

AC:

271

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PVR-related disorder

Benign:1

Mar 13, 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

0.18

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.;.;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.97

D;D;D;D

MetaRNN

Benign

0.0082

T;T;T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.6

.;M;M;.

PhyloP100

2.4

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Uncertain

0.39

Sift

Benign

0.081

T;T;T;T

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.99, 1.0

.;D;D;.

Vest4

0.29

MVP

0.86

MPC

1.2

ClinPred

0.046

GERP RS

4.7

PromoterAI

0.013

Neutral

(source)

gMVP

0.34

Mutation Taster

=100/0

polymorphism

(source)

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

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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