rs16918900

Positions:

• chr8-53234682-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.610+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,257,100 control chromosomes in the GnomAD database, including 1,443 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 0.044 (166 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1277 hom.)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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]

ENSG00000254687 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.610+77G>A		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.610+77G>A		intron_variant			NP_001305426.1
OPRK1	NM_001282904.2	c.343+77G>A		intron_variant			NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.610+77G>A		intron_variant		1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6706 AN: 152138 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0263

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0457

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0447 AC: 49379 AN: 1104844 Hom.: 1277 AF XY: 0.0446 AC XY: 24697 AN XY: 554352

Gnomad4 AFR exome AF: 0.0619

Gnomad4 AMR exome AF: 0.0194

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.000186

Gnomad4 SAS exome AF: 0.0374

Gnomad4 FIN exome AF: 0.0228

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.0438

GnomAD4 genome AF: 0.0440 AC: 6703 AN: 152256 Hom.: 166 Cov.: 32 AF XY: 0.0419 AC XY: 3117 AN XY: 74452

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0205

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0326

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.0457

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0447 Hom.: 147

Bravo AF: 0.0451

Asia WGS AF: 0.0210 AC: 72 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.61

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: rs16918900; hg19: chr8-54147242;