rs702764

Variant names:

• chr8-53229597-T-C
• rs702764
• NM_000912.5:c.843A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-53229597-T-C
• chr8-53229597-T-G

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.843A>G​(p.Ala281Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,832 control chromosomes in the GnomAD database, including 24,604 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 (6190 hom., cov: 32)
  • Exomes 𝑓: 0.14 (18414 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.64
• Publications: 52 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=-0.91).
• BP7: Synonymous conserved (PhyloP=-6.64 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.843A>G	p.Ala281Ala	synonymous_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.843A>G	p.Ala281Ala	synonymous_variant	Exon 4 of 4		NP_001305426.1
OPRK1	NM_001282904.2	c.576A>G	p.Ala192Ala	synonymous_variant	Exon 5 of 5		NP_001269833.1
LOC105375836	NR_188096.1	n.2309T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.843A>G	p.Ala281Ala	synonymous_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36019 AN: 151922 Hom.: 6175 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.223

GnomAD2 exomes AF: 0.170 AC: 42647 AN: 251152 AF XY: 0.159

Gnomad AFR exome AF: 0.493

Gnomad AMR exome AF: 0.280

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.0699

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.144 AC: 210910 AN: 1461792 Hom.: 18414 Cov.: 32 AF XY: 0.142 AC XY: 103262 AN XY: 727188

African (AFR) AF: 0.500 AC: 16737 AN: 33480

American (AMR) AF: 0.278 AC: 12420 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 5003 AN: 26134

East Asian (EAS) AF: 0.0696 AC: 2764 AN: 39700

South Asian (SAS) AF: 0.124 AC: 10676 AN: 86252

European-Finnish (FIN) AF: 0.112 AC: 5979 AN: 53412

Middle Eastern (MID) AF: 0.190 AC: 1097 AN: 5768

European-Non Finnish (NFE) AF: 0.132 AC: 146224 AN: 1111934

Other (OTH) AF: 0.166 AC: 10010 AN: 60396

GnomAD4 genome AF: 0.237 AC: 36083 AN: 152040 Hom.: 6190 Cov.: 32 AF XY: 0.234 AC XY: 17404 AN XY: 74324

African (AFR) AF: 0.485 AC: 20073 AN: 41394

American (AMR) AF: 0.257 AC: 3920 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.0707 AC: 366 AN: 5176

South Asian (SAS) AF: 0.122 AC: 587 AN: 4812

European-Finnish (FIN) AF: 0.106 AC: 1126 AN: 10606

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.129 AC: 8752 AN: 67986

Other (OTH) AF: 0.222 AC: 470 AN: 2114

Alfa AF: 0.162 Hom.: 7580

Bravo AF: 0.260

Asia WGS AF: 0.132 AC: 460 AN: 3478

EpiCase AF: 0.138

EpiControl AF: 0.142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.49
PhyloP100		-6.6
Mutation Taster		=97/3	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: rs702764; hg19: chr8-54142157; COSMIC: COSV108101268;