8-53242895-T-C

Variant names:

• chr8-53242895-T-C
• rs12548098
• ENST00000522508.1:n.275A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.258-7784A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,284,280 control chromosomes in the GnomAD database, including 20,960 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 0.20 (3228 hom., cov: 33)
  • Exomes 𝑓: 0.17 (17732 hom.)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 7 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]

ENSG00000254687 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-7784A>G		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-167A>G		5_prime_UTR_variant	Exon 3 of 5		NP_001269833.1
OPRK1	NM_001318497.2	c.258-7784A>G		intron_variant	Intron 2 of 3		NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-7784A>G		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30149 AN: 151964 Hom.: 3225 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.199

GnomAD2 exomes AF: 0.173 AC: 21884 AN: 126642 AF XY: 0.179

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.0891

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.256

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.171 AC: 194086 AN: 1132198 Hom.: 17732 Cov.: 31 AF XY: 0.174 AC XY: 96390 AN XY: 554874

African (AFR) AF: 0.283 AC: 6851 AN: 24224

American (AMR) AF: 0.0907 AC: 2552 AN: 28132

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 2952 AN: 15792

East Asian (EAS) AF: 0.247 AC: 3119 AN: 12650

South Asian (SAS) AF: 0.223 AC: 16742 AN: 75228

European-Finnish (FIN) AF: 0.171 AC: 2124 AN: 12416

Middle Eastern (MID) AF: 0.189 AC: 829 AN: 4388

European-Non Finnish (NFE) AF: 0.165 AC: 151333 AN: 918058

Other (OTH) AF: 0.184 AC: 7584 AN: 41310

GnomAD4 genome AF: 0.198 AC: 30169 AN: 152082 Hom.: 3228 Cov.: 33 AF XY: 0.200 AC XY: 14853 AN XY: 74350

African (AFR) AF: 0.280 AC: 11614 AN: 41470

American (AMR) AF: 0.127 AC: 1942 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1244 AN: 5156

South Asian (SAS) AF: 0.233 AC: 1120 AN: 4814

European-Finnish (FIN) AF: 0.162 AC: 1717 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11282 AN: 67994

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.186 Hom.: 533

Bravo AF: 0.198

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.88
PhyloP100		-0.19
Mutation Taster		=100/0	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: rs12548098; hg19: chr8-54155455; COSMIC: COSV55570788; COSMIC: COSV55570788;