rs7815824

Positions:

• chr8-53234910-G-A

Variant summary

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

The NM_000912.5(OPRK1):​c.459C>T​(p.Ser153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,614,024 control chromosomes in the GnomAD database, including 1,818 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 0.068 (605 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1213 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.459C>T	p.Ser153=	synonymous_variant	3/4	ENST00000265572.8
OPRK1	NM_001318497.2	c.459C>T	p.Ser153=	synonymous_variant	3/4
OPRK1	NM_001282904.2	c.192C>T	p.Ser64=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.459C>T	p.Ser153=	synonymous_variant	3/4	1	NM_000912.5	P1
	ENST00000524425.1	n.671-7618G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10333 AN: 152024 Hom.: 605 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0593

GnomAD3 exomes AF: 0.0368 AC: 9253 AN: 251400 Hom.: 345 AF XY: 0.0339 AC XY: 4609 AN XY: 135892

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.0524

Gnomad EAS exome AF: 0.0173

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0346

GnomAD4 exome AF: 0.0326 AC: 47670 AN: 1461882 Hom.: 1213 Cov.: 31 AF XY: 0.0315 AC XY: 22887 AN XY: 727242

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.0230

Gnomad4 ASJ exome AF: 0.0569

Gnomad4 EAS exome AF: 0.0156

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0485

Gnomad4 NFE exome AF: 0.0295

Gnomad4 OTH exome AF: 0.0374

GnomAD4 genome AF: 0.0680 AC: 10352 AN: 152142 Hom.: 605 Cov.: 32 AF XY: 0.0664 AC XY: 4944 AN XY: 74404

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.0151

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0521 Hom.: 185

Bravo AF: 0.0724

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.0321

EpiControl AF: 0.0301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.9
DANN	Benign	0.86

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: rs7815824; hg19: chr8-54147470; COSMIC: COSV55571018;