rs9282808
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000912.5(OPRK1):c.1120G>C(p.Asp374His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D374N) has been classified as Benign.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
OPRK1
NM_000912.5 missense
NM_000912.5 missense
Scores
5
14
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.60
Publications
8 publications found
Genes affected
OPRK1 (HGNC:8154): (opioid receptor kappa 1) This gene encodes an opioid receptor, which is a member of the 7 transmembrane-spanning G protein-coupled receptor family. It functions as a receptor for endogenous ligands, as well as a receptor for various synthetic opioids. Ligand binding results in inhibition of adenylate cyclase activity and neurotransmitter release. This opioid receptor plays a role in the perception of pain and mediating the hypolocomotor, analgesic and aversive actions of synthetic opioids. Variations in this gene have also been associated with alcohol dependence and opiate addiction. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study provided evidence for translational readthrough in this gene, and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2017]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22734338).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| OPRK1 | NM_000912.5 | c.1120G>C | p.Asp374His | missense_variant | Exon 4 of 4 | ENST00000265572.8 | NP_000903.2 | |
| OPRK1 | NM_001318497.2 | c.1120G>C | p.Asp374His | missense_variant | Exon 4 of 4 | NP_001305426.1 | ||
| OPRK1 | NM_001282904.2 | c.853G>C | p.Asp285His | missense_variant | Exon 5 of 5 | NP_001269833.1 | ||
| LOC105375836 | NR_188096.1 | n.2032C>G | non_coding_transcript_exon_variant | Exon 3 of 3 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
152208
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.0000120 AC: 3AN: 251002 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
251002
AF XY:
Gnomad AFR exome
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Gnomad EAS exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461530Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727032 show subpopulations
GnomAD4 exome
AF:
AC:
47
AN:
1461530
Hom.:
Cov.:
32
AF XY:
AC XY:
26
AN XY:
727032
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33468
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26116
East Asian (EAS)
AF:
AC:
0
AN:
39694
South Asian (SAS)
AF:
AC:
0
AN:
86212
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5760
European-Non Finnish (NFE)
AF:
AC:
47
AN:
1111774
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.447
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000263 AC: 4AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74358 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
152208
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74358
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41438
American (AMR)
AF:
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5200
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
3
AN:
68042
Other (OTH)
AF:
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.563
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M;.;M
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;N;N
REVEL
Benign
Sift
Uncertain
.;.;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.53
.;.;P;.;P
Vest4
MutPred
0.32
.;.;Loss of disorder (P = 0.0418);.;Loss of disorder (P = 0.0418);
MVP
MPC
0.35
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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