rs7843965

Variant names:

• chr8-53243717-T-C
• rs7843965
• NM_000912.5:c.257+7064A>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+7064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,278 control chromosomes in the GnomAD database, including 834 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 0.10 (834 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.257+7064A>G		intron	N/A	NP_000903.2
	OPRK1	NM_001318497.2		c.257+7064A>G		intron	N/A	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.-184-805A>G		intron	N/A	NP_001269833.1	P41145-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.257+7064A>G		intron	N/A	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000520287.5	TSL:1	c.257+7064A>G		intron	N/A	ENSP00000429706.1	P41145-1
	OPRK1	ENST00000522508.1	TSL:1	n.258-805A>G		intron	N/A	ENSP00000428231.1	E5RJI5

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15208 AN: 152160 Hom.: 833 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0999 AC: 15210 AN: 152278 Hom.: 834 Cov.: 33 AF XY: 0.102 AC XY: 7601 AN XY: 74452

African (AFR) AF: 0.117 AC: 4876 AN: 41566

American (AMR) AF: 0.0588 AC: 899 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3472

East Asian (EAS) AF: 0.166 AC: 863 AN: 5184

South Asian (SAS) AF: 0.179 AC: 860 AN: 4812

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10602

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5985 AN: 68030

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.101 Hom.: 88

Bravo AF: 0.0958

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.015
DANN	Benign	0.77
PhyloP100		-2.9
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: rs7843965; hg19: chr8-54156277;