8-53250826-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000912.5(OPRK1):​c.212T>C​(p.Val71Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69

Publications

0 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30120307).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRK1NM_000912.5 linkc.212T>C p.Val71Ala missense_variant Exon 2 of 4 ENST00000265572.8 NP_000903.2 P41145-1
OPRK1NM_001318497.2 linkc.212T>C p.Val71Ala missense_variant Exon 2 of 4 NP_001305426.1 P41145A0A5F9ZI09
OPRK1NM_001282904.2 linkc.-230T>C 5_prime_UTR_variant Exon 2 of 5 NP_001269833.1 P41145-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPRK1ENST00000265572.8 linkc.212T>C p.Val71Ala missense_variant Exon 2 of 4 1 NM_000912.5 ENSP00000265572.3 P41145-1
OPRK1ENST00000520287.5 linkc.212T>C p.Val71Ala missense_variant Exon 1 of 3 1 ENSP00000429706.1 P41145-1
OPRK1ENST00000522508.1 linkn.212T>C non_coding_transcript_exon_variant Exon 2 of 5 1 ENSP00000428231.1 E5RJI5
OPRK1ENST00000673285.2 linkc.212T>C p.Val71Ala missense_variant Exon 2 of 4 ENSP00000500765.2 A0A5F9ZI09

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000810
AC:
2
AN:
246986
AF XY:
0.00000746
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000585
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459192
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
725912
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33064
American (AMR)
AF:
0.0000449
AC:
2
AN:
44578
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26036
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39432
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85934
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53286
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5750
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1110840
Other (OTH)
AF:
0.0000166
AC:
1
AN:
60272
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.212T>C (p.V71A) alteration is located in exon 2 (coding exon 1) of the OPRK1 gene. This alteration results from a T to C substitution at nucleotide position 212, causing the valine (V) at amino acid position 71 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.23
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
.;T;T
Eigen
Benign
-0.012
Eigen_PC
Benign
0.14
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.60
T;.;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.30
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
.;M;M
PhyloP100
5.7
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.7
.;N;N
REVEL
Benign
0.27
Sift
Benign
0.27
.;T;T
Sift4G
Benign
0.20
T;T;T
Polyphen
0.048
.;B;B
Vest4
0.61
MutPred
0.54
.;Loss of stability (P = 0.126);Loss of stability (P = 0.126);
MVP
0.79
MPC
0.61
ClinPred
0.68
D
GERP RS
4.9
Varity_R
0.56
gMVP
0.56
Mutation Taster
=34/66
disease causing

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

Other links and lift over

dbSNP: rs756967929; hg19: chr8-54163386; API