rs1051660

chr8-53251002-C-Achr8-53251002-C-Gchr8-53251002-C-T

Variant summary

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

The NM_000912.5(OPRK1):c.36G>T(p.Pro12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,574,264 control chromosomes in the GnomAD database, including 8,124 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 0.094 (754 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7370 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.36G>T	p.Pro12=	synonymous_variant	2/4	ENST00000265572.8
OPRK1	NM_001318497.2	c.36G>T	p.Pro12=	synonymous_variant	2/4
OPRK1	NM_001282904.2	c.-406G>T		5_prime_UTR_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.36G>T	p.Pro12=	synonymous_variant	2/4	1	NM_000912.5	P1
OPRK1	ENST00000520287.5	c.36G>T	p.Pro12=	synonymous_variant	1/3	1		P1
OPRK1	ENST00000522508.1	c.36G>T	p.Pro12=	synonymous_variant, NMD_transcript_variant	2/5	1
OPRK1	ENST00000673285.2	c.36G>T	p.Pro12=	synonymous_variant	2/4

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14357 AN: 152126 Hom.: 753 Cov.: 33

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0899

GnomAD3 exomes AF: 0.113 AC: 20400 AN: 180668 Hom.: 1262 AF XY: 0.120 AC XY: 11839 AN XY: 98780

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0963

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0975 AC: 138684 AN: 1422020 Hom.: 7370 Cov.: 32 AF XY: 0.100 AC XY: 70708 AN XY: 703986

Gnomad4 AFR exome AF: 0.0964

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0896

Gnomad4 OTH exome AF: 0.105

GnomAD4 genome AF: 0.0943 AC: 14360 AN: 152244 Hom.: 754 Cov.: 33 AF XY: 0.0967 AC XY: 7199 AN XY: 74430

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.0560

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0877

Gnomad4 OTH AF: 0.0889

Alfa AF: 0.0427 Hom.: 133

Bravo AF: 0.0895

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.8
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1051660; hg19: chr8-54163562; COSMIC: COSV55569026;