dbSNP rs1563326168: OPRK1:p.Met226Val (chr8-53229764-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000912.5(OPRK1):c.676A>G(p.Met226Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. M226L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.16

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]

OPRK1 links:

LOC105375836 (HGNC:):

LOC105375836 links:

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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=0.22892264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5 link	c.676A>G	p.Met226Val	missense_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2	P41145-1
OPRK1	NM_001318497.2 link	c.676A>G	p.Met226Val	missense_variant	Exon 4 of 4		NP_001305426.1	P41145A0A5F9ZI09
OPRK1	NM_001282904.2 link	c.409A>G	p.Met137Val	missense_variant	Exon 5 of 5		NP_001269833.1	P41145-2
LOC105375836	NR_188096.1 link	n.2476T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8 link	c.676A>G	p.Met226Val	missense_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3		P41145-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460818

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726668

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86086

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111502

Other (OTH)

AF:

0.00

AC:

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.060

.;.;T;.;T

Eigen

Benign

-0.14

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;T;.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.73

.;.;N;.;N

PhyloP100

4.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.52

.;.;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.56

.;.;T;T;T

Sift4G

Benign

0.70

T;T;T;T;T

Polyphen

0.0

.;.;B;.;B

Vest4

0.35

MutPred

0.59

.;.;Gain of methylation at K227 (P = 0.0365);.;Gain of methylation at K227 (P = 0.0365);

MVP

0.74

MPC

0.30

ClinPred

0.43

GERP RS

4.5

Varity_R

0.28

gMVP

0.85

Mutation Taster

=26/74

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1563326168

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over