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GeneBe

rs11540085

chr19-44644096-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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 (★).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)
Exomes 𝑓: 0.019 ( 315 hom. )

Consequence

PVR
NM_006505.5 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.238
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]
CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-44644096-C-T is Benign according to our data. Variant chr19-44644096-C-T is described in ClinVar as [Benign]. Clinvar id is 3041859.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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 male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PVRNM_006505.5 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/8 ENST00000425690.8
PVRNM_001135768.3 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/8
PVRNM_001135769.3 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/7
PVRNM_001135770.4 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PVRENST00000425690.8 linkuse as main transcriptc.-1C>T 5_prime_UTR_variant 1/81 NM_006505.5 P2
CEACAM16-AS1ENST00000662585.1 linkuse as main transcriptn.476-11477G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0124
AC:
1887
AN:
152188
Hom.:
19
Cov.:
32
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
GnomAD3 exomes
AF:
0.0118
AC:
1296
AN:
110010
Hom.:
19
AF XY:
0.0118
AC XY:
716
AN XY:
60688
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 SAS exome
AF:
0.00360
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.:
31
AF XY:
0.0188
AC XY:
12628
AN XY:
672096
show subpopulations
Gnomad4 AFR exome
AF:
0.00261
Gnomad4 AMR exome
AF:
0.00566
Gnomad4 ASJ exome
AF:
0.0152
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00384
Gnomad4 FIN exome
AF:
0.00932
Gnomad4 NFE exome
AF:
0.0227
Gnomad4 OTH exome
AF:
0.0146
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0124
AC:
1887
AN:
152306
Hom.:
19
Cov.:
32
AF XY:
0.0118
AC XY:
879
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00332
Gnomad4 AMR
AF:
0.0112
Gnomad4 ASJ
AF:
0.0193
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00649
Gnomad4 NFE
AF:
0.0202
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.0164
Hom.:
7
Bravo
AF:
0.0120
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

PVR-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 14, 2020This 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
14
Dann
Benign
0.86
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11540085; hg19: chr19-45147396; COSMIC: COSV51824528; COSMIC: COSV51824528; API