rs16918875

Variant names:

• chr8-53229594-G-A
• rs16918875
• NM_000912.5:c.846C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000912.5(OPRK1):​c.846C>T​(p.Val282Val) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.846C>T	p.Val282Val	synonymous	Exon 4 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.846C>T	p.Val282Val	synonymous	Exon 4 of 4	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.579C>T	p.Val193Val	synonymous	Exon 5 of 5	NP_001269833.1	P41145-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.846C>T	p.Val282Val	synonymous	Exon 4 of 4	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000520287.5	TSL:1	c.846C>T	p.Val282Val	synonymous	Exon 3 of 3	ENSP00000429706.1	P41145-1
	OPRK1	ENST00000524278.5	TSL:1	c.579C>T	p.Val193Val	synonymous	Exon 3 of 3	ENSP00000430923.1	P41145-2

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

GnomAD2 exomes AF: 0.0429 AC: 10772 AN: 251210 AF XY: 0.0419

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 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

African (AFR) AF: 0.153 AC: 5124 AN: 33478

American (AMR) AF: 0.0251 AC: 1124 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 491 AN: 26134

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0372 AC: 3211 AN: 86254

European-Finnish (FIN) AF: 0.0231 AC: 1233 AN: 53410

Middle Eastern (MID) AF: 0.0425 AC: 245 AN: 5768

European-Non Finnish (NFE) AF: 0.0514 AC: 57175 AN: 1111966

Other (OTH) AF: 0.0508 AC: 3068 AN: 60396

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

African (AFR) AF: 0.149 AC: 6201 AN: 41484

American (AMR) AF: 0.0379 AC: 580 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0328 AC: 158 AN: 4818

European-Finnish (FIN) AF: 0.0189 AC: 201 AN: 10620

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0465 AC: 3162 AN: 68008

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0536 Hom.: 459

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.025
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16918875; hg19: chr8-54142154; COSMIC: COSV108101267;