rs7836120

Variant names:

• chr8-53244979-T-C
• rs7836120
• NM_000912.5:c.257+5802A>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.257+5802A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,188 control chromosomes in the GnomAD database, including 4,537 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 0.22 (4537 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+5802A>G		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.257+5802A>G		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-184-2067A>G		intron_variant	Intron 2 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.257+5802A>G		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000520287.5	c.257+5802A>G		intron_variant	Intron 1 of 2	1		ENSP00000429706.1
OPRK1	ENST00000522508.1	n.258-2067A>G		intron_variant	Intron 2 of 4	1		ENSP00000428231.1
OPRK1	ENST00000673285.2	c.257+5802A>G		intron_variant	Intron 2 of 3			ENSP00000500765.2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34196 AN: 152070 Hom.: 4524 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.225 AC: 34233 AN: 152188 Hom.: 4537 Cov.: 32 AF XY: 0.226 AC XY: 16799 AN XY: 74424

African (AFR) AF: 0.372 AC: 15454 AN: 41490

American (AMR) AF: 0.135 AC: 2064 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 662 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1253 AN: 5178

South Asian (SAS) AF: 0.232 AC: 1119 AN: 4814

European-Finnish (FIN) AF: 0.163 AC: 1733 AN: 10614

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11312 AN: 68012

Other (OTH) AF: 0.219 AC: 463 AN: 2112

Alfa AF: 0.181 Hom.: 3817

Bravo AF: 0.228

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.35
PhyloP100		-2.4
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: rs7836120; hg19: chr8-54157539;