rs963549

Positions:

• chr8-53229264-C-T

Variant summary

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

The NM_000912.5(OPRK1):​c.*33G>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 0.153 in 1,583,424 control chromosomes in the GnomAD database, including 23,920 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 (6010 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17910 hom.)
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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]

LOC105375836 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.*33G>A		3_prime_UTR_variant	4/4	ENST00000265572.8
LOC105375836	XR_928877.2	n.1976C>T		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001318497.2	c.1176G>A	p.Ser392=	synonymous_variant	4/4
OPRK1	NM_001282904.2	c.*33G>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.*33G>A		3_prime_UTR_variant	4/4	1	NM_000912.5	P1
	ENST00000524425.1	n.670+12760C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35689 AN: 151964 Hom.: 5995 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.171 AC: 39842 AN: 232842 Hom.: 4641 AF XY: 0.160 AC XY: 19891 AN XY: 124606

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0702

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.144 AC: 206233 AN: 1431342 Hom.: 17910 Cov.: 31 AF XY: 0.142 AC XY: 100527 AN XY: 708000

Gnomad4 AFR exome AF: 0.490

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.192

Gnomad4 EAS exome AF: 0.0701

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.235 AC: 35750 AN: 152082 Hom.: 6010 Cov.: 32 AF XY: 0.232 AC XY: 17257 AN XY: 74352

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0701

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.222

Alfa AF: 0.155 Hom.: 3168

Bravo AF: 0.258

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.018
DANN	Benign	0.78

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: rs963549; hg19: chr8-54141824; COSMIC: COSV55569767;