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GeneBe

19-44647491-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_006505.5(PVR):c.348G>A(p.Glu116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00859 in 1,614,064 control chromosomes in the GnomAD database, including 1,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.044 ( 540 hom., cov: 30)
Exomes 𝑓: 0.0049 ( 485 hom. )

Consequence

PVR
NM_006505.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.58
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-44647491-G-A is Benign according to our data. Variant chr19-44647491-G-A is described in ClinVar as [Benign]. Clinvar id is 3038290.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-3.58 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PVRNM_006505.5 linkuse as main transcriptc.348G>A p.Glu116= synonymous_variant 2/8 ENST00000425690.8
PVRNM_001135770.4 linkuse as main transcriptc.348G>A p.Glu116= synonymous_variant 2/6
PVRNM_001135768.3 linkuse as main transcriptc.348G>A p.Glu116= synonymous_variant 2/8
PVRNM_001135769.3 linkuse as main transcriptc.348G>A p.Glu116= synonymous_variant 2/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PVRENST00000425690.8 linkuse as main transcriptc.348G>A p.Glu116= synonymous_variant 2/81 NM_006505.5 P2
CEACAM16-AS1ENST00000662585.1 linkuse as main transcriptn.476-14872C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0442
AC:
6719
AN:
152106
Hom.:
534
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.151
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0206
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0159
Gnomad NFE
AF:
0.000808
Gnomad OTH
AF:
0.0325
GnomAD3 exomes
AF:
0.0121
AC:
2998
AN:
248764
Hom.:
209
AF XY:
0.00868
AC XY:
1169
AN XY:
134728
show subpopulations
Gnomad AFR exome
AF:
0.156
Gnomad AMR exome
AF:
0.00886
Gnomad ASJ exome
AF:
0.00338
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000791
Gnomad OTH exome
AF:
0.00637
GnomAD4 exome
AF:
0.00486
AC:
7111
AN:
1461840
Hom.:
485
Cov.:
32
AF XY:
0.00420
AC XY:
3052
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.157
Gnomad4 AMR exome
AF:
0.00962
Gnomad4 ASJ exome
AF:
0.00298
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000483
Gnomad4 OTH exome
AF:
0.0113
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0444
AC:
6752
AN:
152224
Hom.:
540
Cov.:
30
AF XY:
0.0437
AC XY:
3255
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.152
Gnomad4 AMR
AF:
0.0206
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00104
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000809
Gnomad4 OTH
AF:
0.0322
Alfa
AF:
0.00959
Hom.:
157
Bravo
AF:
0.0501
Asia WGS
AF:
0.0140
AC:
48
AN:
3478
EpiCase
AF:
0.000709
EpiControl
AF:
0.000949

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 SciencesApr 01, 2019This 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
-0.88
Cadd
Benign
0.93
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

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

Other links and lift over

dbSNP: rs10421291; hg19: chr19-45150763; COSMIC: COSV51824373; COSMIC: COSV51824373; API