rs12548098

Positions:

• chr8-53242895-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.258-7784A>G variant causes a intron 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_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.258-7784A>G		intron_variant		ENST00000265572.8
OPRK1	NM_001282904.2	c.-167A>G		5_prime_UTR_variant	3/5
OPRK1	NM_001318497.2	c.258-7784A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-7784A>G		intron_variant		1	NM_000912.5	P1
OPRK1	ENST00000520287.5	c.258-7784A>G		intron_variant		1		P1
OPRK1	ENST00000522508.1	c.275A>G	p.Lys92Arg	missense_variant, NMD_transcript_variant	3/5	1
OPRK1	ENST00000673285.2	c.258-7784A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30149 AN: 151964 Hom.: 3225 Cov.: 33

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

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.: 31 AF XY: 0.174 AC XY: 96390 AN XY: 554874

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.: 33 AF XY: 0.200 AC XY: 14853 AN XY: 74350

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

Other links and lift over

dbSNP: rs12548098; hg19: chr8-54155455; COSMIC: COSV55570788; COSMIC: COSV55570788;