rs7826614

Positions:

• chr8-53244866-G-A
• chr8-53244866-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.257+5915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,002 control chromosomes in the GnomAD database, including 3,271 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 (3271 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

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

Verdict is Benign. Variant got -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 = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+5915C>T		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-184-1954C>T		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.257+5915C>T		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.257+5915C>T		intron_variant		1	NM_000912.5	ENSP00000265572	P1
OPRK1	ENST00000520287.5	c.257+5915C>T		intron_variant		1		ENSP00000429706	P1
OPRK1	ENST00000522508.1	c.258-1954C>T		intron_variant, NMD_transcript_variant		1		ENSP00000428231
OPRK1	ENST00000673285.2	c.257+5915C>T		intron_variant				ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30231 AN: 151884 Hom.: 3269 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.199 AC: 30249 AN: 152002 Hom.: 3271 Cov.: 32 AF XY: 0.200 AC XY: 14887 AN XY: 74300

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.198

Alfa AF: 0.0866 Hom.: 127

Bravo AF: 0.199

Asia WGS AF: 0.261 AC: 908 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	2.5
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs7826614; hg19: chr8-54157426;