chr8-53229320-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000912.5(OPRK1):ā€‹c.1120G>Cā€‹(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. 14/21 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. D374N) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000032 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.60
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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/exons MANE Protein UniProt
OPRK1NM_000912.5 linkc.1120G>C p.Asp374His missense_variant 4/4 ENST00000265572.8 NP_000903.2 P41145-1
OPRK1NM_001318497.2 linkc.1120G>C p.Asp374His missense_variant 4/4 NP_001305426.1 P41145A0A5F9ZI09
OPRK1NM_001282904.2 linkc.853G>C p.Asp285His missense_variant 5/5 NP_001269833.1 P41145-2
LOC105375836NR_188096.1 linkn.2032C>G non_coding_transcript_exon_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OPRK1ENST00000265572.8 linkc.1120G>C p.Asp374His missense_variant 4/41 NM_000912.5 ENSP00000265572.3 P41145-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
251002
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135634
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461530
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
727032
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000423
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00000765
Hom.:
7
Bravo
AF:
0.0000340
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
.;.;T;.;T
Eigen
Benign
-0.042
Eigen_PC
Benign
-0.067
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.84
T;T;.;.;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.23
T;T;T;T;T
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.2
.;.;M;.;M
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.8
.;.;N;N;N
REVEL
Benign
0.20
Sift
Uncertain
0.020
.;.;D;D;D
Sift4G
Uncertain
0.010
D;D;D;D;D
Polyphen
0.53
.;.;P;.;P
Vest4
0.12
MutPred
0.32
.;.;Loss of disorder (P = 0.0418);.;Loss of disorder (P = 0.0418);
MVP
0.87
MPC
0.35
ClinPred
0.35
T
GERP RS
5.8
Varity_R
0.10
gMVP
0.35

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: rs9282808; hg19: chr8-54141880; API