dbSNP rs3802281: OPRK1:c.*694A>G (chr8-53228603-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000912.5(OPRK1):c.*694A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,232 control chromosomes in the GnomAD database, including 6,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 6224 hom., cov: 32)

Exomes 𝑓: 0.14 ( 1 hom. )

Consequence

OPRK1
NM_000912.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.337

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5 link	c.*694A>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2	P41145-1
LOC105375836	NR_188096.1 link	n.1315T>C	non_coding_transcript_exon_variant	Exon 3 of 3
OPRK1	NM_001318497.2 link	c.*607A>G	3_prime_UTR_variant	Exon 4 of 4		NP_001305426.1	P41145A0A5F9ZI09
OPRK1	NM_001282904.2 link	c.*694A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1	P41145-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPRK1	ENST00000265572.8 link	c.*694A>G	3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3	P41145-1
OPRK1	ENST00000673285.2 link	c.*607A>G	3_prime_UTR_variant	Exon 4 of 4			ENSP00000500765.2	A0A5F9ZI09
ENSG00000254687	ENST00000524425.1 link	n.670+12099T>C	intron_variant	Intron 2 of 2	3
OPRK1	ENST00000522508.1 link	n.*1660A>G	downstream_gene_variant		1		ENSP00000428231.1	E5RJI5

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36924

AN:

152100

Hom.:

6212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.0708

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.143

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.243

AC:

36985

AN:

152218

Hom.:

6224

Cov.:

AF XY:

0.240

AC XY:

17858

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.476

AC:

19735

AN:

41480

American (AMR)

AF:

0.265

AC:

4056

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

699

AN:

3470

East Asian (EAS)

AF:

0.0705

AC:

366

AN:

5188

South Asian (SAS)

AF:

0.137

AC:

660

AN:

4824

European-Finnish (FIN)

AF:

0.109

AC:

1152

AN:

10608

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.142

AC:

9682

AN:

68024

Other (OTH)

AF:

0.230

AC:

487

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1284

2568

3853

5137

6421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.176

Hom.:

11305

Bravo

AF:

0.265

Asia WGS

AF:

0.134

AC:

466

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.98

(source)

DANN

Benign

0.71

PhyloP100

-0.34

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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