19-44647342-G-A
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The ENST00000425690.8(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. 15/19 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
ENST00000425690.8 missense
ENST00000425690.8 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -1.55
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PVR | NM_006505.5 | c.199G>A | p.Ala67Thr | missense_variant | 2/8 | ENST00000425690.8 | NP_006496.4 | |
PVR | NM_001135770.4 | c.199G>A | p.Ala67Thr | missense_variant | 2/6 | NP_001129242.2 | ||
PVR | NM_001135768.3 | c.199G>A | p.Ala67Thr | missense_variant | 2/8 | NP_001129240.1 | ||
PVR | NM_001135769.3 | c.199G>A | p.Ala67Thr | missense_variant | 2/7 | NP_001129241.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PVR | ENST00000425690.8 | c.199G>A | p.Ala67Thr | missense_variant | 2/8 | 1 | NM_006505.5 | ENSP00000402060 | P2 | |
CEACAM16-AS1 | ENST00000662585.1 | n.476-14723C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0580 AC: 8821AN: 152138Hom.: 331 Cov.: 30
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GnomAD3 exomes AF: 0.0774 AC: 19250AN: 248850Hom.: 1056 AF XY: 0.0788 AC XY: 10607AN XY: 134626
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GnomAD4 exome AF: 0.0591 AC: 86357AN: 1460842Hom.: 3724 Cov.: 32 AF XY: 0.0620 AC XY: 45049AN XY: 726638
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GnomAD4 genome AF: 0.0580 AC: 8830AN: 152256Hom.: 331 Cov.: 30 AF XY: 0.0599 AC XY: 4459AN XY: 74444
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
PVR-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 01, 2019 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;N;N;.
MutationTaster
Benign
P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0
.;B;B;.
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at