dbSNP rs11540085: PVR:c.-1C>T (chr19-44644096-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_006505.5(PVR):c.-1C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,514,500 control chromosomes in the GnomAD database, including 334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.019 ( 315 hom. )

Consequence

PVR
NM_006505.5 5_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.238

Publications

1 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 -9 ACMG points.

BP6

Variant 19-44644096-C-T is Benign according to our data. Variant chr19-44644096-C-T is described in ClinVar as Benign. ClinVar VariationId is 3041859.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0124 (1887/152306) while in subpopulation NFE AF = 0.0202 (1374/68016). AF 95% confidence interval is 0.0193. There are 19 homozygotes in GnomAd4. There are 879 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5 link	c.-1C>T	5_prime_UTR_variant	Exon 1 of 8	ENST00000425690.8	NP_006496.4	P15151A0A0C4DG49A8K4I1
PVR	NM_001135770.4 link	c.-1C>T	5_prime_UTR_variant	Exon 1 of 6		NP_001129242.2	P15151A0A0A0MSA9
PVR	NM_001135768.3 link	c.-1C>T	5_prime_UTR_variant	Exon 1 of 8		NP_001129240.1	P15151-2
PVR	NM_001135769.3 link	c.-1C>T	5_prime_UTR_variant	Exon 1 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.-1C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_006505.5	ENSP00000402060.2		A0A0C4DG49

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1887

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00649

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.0118

AC:

1296

AN:

110010

AF XY:

0.0118

show subpopulations

Gnomad AFR exome

AF:

0.00422

Gnomad AMR exome

AF:

0.00569

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00671

Gnomad NFE exome

AF:

0.0220

Gnomad OTH exome

AF:

0.0112

GnomAD4 exome

AF:

0.0194

AC:

26420

AN:

1362194

Hom.:

315

Cov.:

AF XY:

0.0188

AC XY:

12628

AN XY:

672096

show subpopulations

African (AFR)

AF:

0.00261

AC:

AN:

28314

American (AMR)

AF:

0.00566

AC:

191

AN:

33764

Ashkenazi Jewish (ASJ)

AF:

0.0152

AC:

368

AN:

24212

East Asian (EAS)

AF:

0.00

AC:

AN:

32322

South Asian (SAS)

AF:

0.00384

AC:

296

AN:

77140

European-Finnish (FIN)

AF:

0.00932

AC:

330

AN:

35410

Middle Eastern (MID)

AF:

0.00409

AC:

AN:

4646

European-Non Finnish (NFE)

AF:

0.0227

AC:

24310

AN:

1069460

Other (OTH)

AF:

0.0146

AC:

832

AN:

56926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1288

2576

3863

5151

6439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

946

1892

2838

3784

4730

<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:

0.0124

AC:

1887

AN:

152306

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

879

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00332

AC:

138

AN:

41574

American (AMR)

AF:

0.0112

AC:

172

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00186

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00649

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0202

AC:

1374

AN:

68016

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00231

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

Feb 14, 2020

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

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

-0.24

PromoterAI

0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=298/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -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