chr1-28859294-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000911.4(OPRD1):​c.568C>G​(p.Arg190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R190C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

OPRD1
NM_000911.4 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.87
Variant links:
Genes affected
OPRD1 (HGNC:8153): (opioid receptor delta 1) Enables G protein-coupled enkephalin receptor activity. Involved in several processes, including G protein-coupled opioid receptor signaling pathway; cellular response to hypoxia; and positive regulation of peptidyl-serine phosphorylation. Is intrinsic component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28015265).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRD1NM_000911.4 linkc.568C>G p.Arg190Gly missense_variant Exon 2 of 3 ENST00000234961.7 NP_000902.3 P41143

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPRD1ENST00000234961.7 linkc.568C>G p.Arg190Gly missense_variant Exon 2 of 3 1 NM_000911.4 ENSP00000234961.2 P41143

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459712
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726002
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.49
.;T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.38
.;N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-2.9
.;D
REVEL
Benign
0.087
Sift
Uncertain
0.020
.;D
Sift4G
Benign
0.18
T;T
Polyphen
0.0010
.;B
Vest4
0.45
MutPred
0.44
Gain of catalytic residue at R190 (P = 0.0398);Gain of catalytic residue at R190 (P = 0.0398);
MVP
0.65
MPC
1.0
ClinPred
0.40
T
GERP RS
3.7
Varity_R
0.33
gMVP
0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-29185806; API