rs16918875

chr8-53229594-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.846C>T(p.Val282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,614,034 control chromosomes in the GnomAD database, including 2,711 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 0.069 (546 hom., cov: 32)
  • Exomes 𝑓: 0.049 (2165 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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=-0.57).
• BP7: Synonymous conserved (PhyloP=0.025 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.846C>T	p.Val282=	synonymous_variant	4/4	ENST00000265572.8
LOC105375836	XR_928877.2	n.2306G>A		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001318497.2	c.846C>T	p.Val282=	synonymous_variant	4/4
OPRK1	NM_001282904.2	c.579C>T	p.Val193=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.846C>T	p.Val282=	synonymous_variant	4/4	1	NM_000912.5	P1
	ENST00000524425.1	n.671-12934G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10523 AN: 152088 Hom.: 545 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0189

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0579

GnomAD3 exomes AF: 0.0429 AC: 10772 AN: 251210 Hom.: 380 AF XY: 0.0419 AC XY: 5688 AN XY: 135772

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0179

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.0369

Gnomad FIN exome AF: 0.0208

Gnomad NFE exome AF: 0.0477

Gnomad OTH exome AF: 0.0434

GnomAD4 exome AF: 0.0490 AC: 71681 AN: 1461828 Hom.: 2165 Cov.: 32 AF XY: 0.0485 AC XY: 35297 AN XY: 727214

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0251

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0372

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0514

Gnomad4 OTH exome AF: 0.0508

GnomAD4 genome AF: 0.0692 AC: 10534 AN: 152206 Hom.: 546 Cov.: 32 AF XY: 0.0672 AC XY: 5004 AN XY: 74420

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0379

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0328

Gnomad4 FIN AF: 0.0189

Gnomad4 NFE AF: 0.0465

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0514 Hom.: 325

Bravo AF: 0.0738

Asia WGS AF: 0.0280 AC: 98 AN: 3478

EpiCase AF: 0.0466

EpiControl AF: 0.0495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	2.5
Dann	Benign	0.79

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: rs16918875; hg19: chr8-54142154;