rs702764

Positions:

• chr8-53229597-T-C
• chr8-53229597-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000912.5(OPRK1):​c.843A>G​(p.Ala281=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,832 control chromosomes in the GnomAD database, including 24,604 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 (6190 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18414 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.64

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-6.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.843A>G	p.Ala281=	synonymous_variant	4/4	ENST00000265572.8
LOC105375836	XR_928877.2	n.2309T>C		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001318497.2	c.843A>G	p.Ala281=	synonymous_variant	4/4
OPRK1	NM_001282904.2	c.576A>G	p.Ala192=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.843A>G	p.Ala281=	synonymous_variant	4/4	1	NM_000912.5	P1
	ENST00000524425.1	n.671-12931T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36019 AN: 151922 Hom.: 6175 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.170 AC: 42647 AN: 251152 Hom.: 4915 AF XY: 0.159 AC XY: 21537 AN XY: 135766

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0699

Gnomad SAS exome AF: 0.125

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.144 AC: 210910 AN: 1461792 Hom.: 18414 Cov.: 32 AF XY: 0.142 AC XY: 103262 AN XY: 727188

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.0696

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.237 AC: 36083 AN: 152040 Hom.: 6190 Cov.: 32 AF XY: 0.234 AC XY: 17404 AN XY: 74324

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.222

Alfa AF: 0.154 Hom.: 2965

Bravo AF: 0.260

Asia WGS AF: 0.132 AC: 460 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.49

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: rs702764; hg19: chr8-54142157;