Genetic Variant OPRK1:c.*1068G>A (chr8-53228229-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000912.5(OPRK1):c.*1068G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,126 control chromosomes in the GnomAD database, including 3,119 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 0.17 ( 3119 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

OPRK1
NM_000912.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0310

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5 link	c.*1068G>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2	P41145-1
OPRK1	NM_001318497.2 link	c.*981G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001305426.1	P41145A0A5F9ZI09
OPRK1	NM_001282904.2 link	c.*1068G>A	3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1	P41145-2
LOC105375836	NR_188096.1 link	n.941C>T	non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPRK1	ENST00000265572 link	c.*1068G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3	P41145-1
OPRK1	ENST00000673285 link	c.*981G>A	3_prime_UTR_variant	Exon 4 of 4			ENSP00000500765.2	A0A5F9ZI09
ENSG00000254687	ENST00000524425.1 link	n.670+11725C>T	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26469

AN:

152008

Hom.:

3111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.0701

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0895

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0959

Gnomad OTH

AF:

0.173

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.174

AC:

26515

AN:

152126

Hom.:

3119

Cov.:

AF XY:

0.174

AC XY:

12918

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.327

Gnomad4 AMR

AF:

0.231

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.0699

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.0895

Gnomad4 NFE

AF:

0.0959

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.108

Hom.:

1763

Bravo

AF:

0.193

Asia WGS

AF:

0.106

AC:

368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.57

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over