Variant chr8-53242895-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001282904.2(OPRK1):c.-167A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,284,280 control chromosomes in the GnomAD database, including 20,960 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 0.20 ( 3228 hom., cov: 33)

Exomes 𝑓: 0.17 ( 17732 hom. )

Consequence

OPRK1
NM_001282904.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.189

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:

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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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5 linkuse as main transcript	c.258-7784A>G	intron_variant		ENST00000265572.8	NP_000903.2	P41145-1
OPRK1	NM_001282904.2 linkuse as main transcript	c.-167A>G	5_prime_UTR_variant	3/5		NP_001269833.1	P41145-2
OPRK1	NM_001318497.2 linkuse as main transcript	c.258-7784A>G	intron_variant			NP_001305426.1	P41145A0A5F9ZI09

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPRK1	ENST00000265572.8 linkuse as main transcript	c.258-7784A>G	intron_variant		1	NM_000912.5	ENSP00000265572.3	P41145-1
OPRK1	ENST00000520287.5 linkuse as main transcript	c.258-7784A>G	intron_variant		1		ENSP00000429706.1	P41145-1
OPRK1	ENST00000522508.1 linkuse as main transcript	n.275A>G	non_coding_transcript_exon_variant	3/5	1		ENSP00000428231.1	E5RJI5
OPRK1	ENST00000673285.2 linkuse as main transcript	c.258-7784A>G	intron_variant				ENSP00000500765.2	A0A5F9ZI09

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30149

AN:

151964

Hom.:

3225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.280

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.241

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.173

AC:

21884

AN:

126642

Hom.:

2226

AF XY:

0.179

AC XY:

12433

AN XY:

69286

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.171

AC:

194086

AN:

1132198

Hom.:

17732

Cov.:

AF XY:

0.174

AC XY:

96390

AN XY:

554874

show subpopulations

Gnomad4 AFR exome

AF:

0.283

Gnomad4 AMR exome

AF:

0.0907

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.171

Gnomad4 NFE exome

AF:

0.165

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.198

AC:

30169

AN:

152082

Hom.:

3228

Cov.:

AF XY:

0.200

AC XY:

14853

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.191

Gnomad4 EAS

AF:

0.241

Gnomad4 SAS

AF:

0.233

Gnomad4 FIN

AF:

0.162

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.186

Hom.:

533

Bravo

AF:

0.198

Asia WGS

AF:

0.261

AC:

909

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.8

DANN

Benign

0.88

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