8-53229264-C-T

Variant names:

• chr8-53229264-C-T
• rs963549
• ENST00000522508.1:n.*999G>A

Variant summary

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

The ENST00000522508.1(OPRK1):​n.*999G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,583,424 control chromosomes in the GnomAD database, including 23,920 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 0.24 (6010 hom., cov: 32)
  • Exomes 𝑓: 0.14 (17910 hom.)
• Consequence: OPRK1 ENST00000522508.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 35 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*33G>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.1176G>A	p.Ser392Ser	synonymous_variant	Exon 4 of 4		NP_001305426.1
LOC105375836	NR_188096.1	n.1976C>T		non_coding_transcript_exon_variant	Exon 3 of 3
OPRK1	NM_001282904.2	c.*33G>A		3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*33G>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35689 AN: 151964 Hom.: 5995 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.171 AC: 39842 AN: 232842 AF XY: 0.160

Gnomad AFR exome AF: 0.483

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.186

Gnomad EAS exome AF: 0.0702

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.144 AC: 206233 AN: 1431342 Hom.: 17910 Cov.: 31 AF XY: 0.142 AC XY: 100527 AN XY: 708000

African (AFR) AF: 0.490 AC: 16044 AN: 32776

American (AMR) AF: 0.279 AC: 11928 AN: 42746

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 4630 AN: 24168

East Asian (EAS) AF: 0.0701 AC: 2761 AN: 39370

South Asian (SAS) AF: 0.123 AC: 9965 AN: 80930

European-Finnish (FIN) AF: 0.112 AC: 5843 AN: 52306

Middle Eastern (MID) AF: 0.191 AC: 988 AN: 5172

European-Non Finnish (NFE) AF: 0.132 AC: 144346 AN: 1094862

Other (OTH) AF: 0.165 AC: 9728 AN: 59012

GnomAD4 genome AF: 0.235 AC: 35750 AN: 152082 Hom.: 6010 Cov.: 32 AF XY: 0.232 AC XY: 17257 AN XY: 74352

African (AFR) AF: 0.476 AC: 19695 AN: 41416

American (AMR) AF: 0.258 AC: 3945 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.0701 AC: 363 AN: 5178

South Asian (SAS) AF: 0.121 AC: 586 AN: 4824

European-Finnish (FIN) AF: 0.106 AC: 1123 AN: 10590

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8778 AN: 67994

Other (OTH) AF: 0.222 AC: 469 AN: 2108

Alfa AF: 0.167 Hom.: 4888

Bravo AF: 0.258

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.018
DANN	Benign	0.78
PhyloP100		-2.3
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: rs963549; hg19: chr8-54141824; COSMIC: COSV55569767;