chr8-53239818-T-C

Variant names:

• chr8-53239818-T-C
• rs997917
• NM_000912.5:c.258-4707A>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.258-4707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,068 control chromosomes in the GnomAD database, including 16,179 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 0.43 (16179 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943
• Publications: 27 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]

ENSG00000254687 (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 = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-4707A>G		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.258-4707A>G		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-11+2921A>G		intron_variant	Intron 3 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-4707A>G		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64646 AN: 151950 Hom.: 16127 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.426 AC: 64755 AN: 152068 Hom.: 16179 Cov.: 33 AF XY: 0.427 AC XY: 31718 AN XY: 74322

African (AFR) AF: 0.702 AC: 29089 AN: 41464

American (AMR) AF: 0.384 AC: 5869 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1690 AN: 3472

East Asian (EAS) AF: 0.362 AC: 1872 AN: 5178

South Asian (SAS) AF: 0.444 AC: 2140 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3059 AN: 10560

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19792 AN: 67978

Other (OTH) AF: 0.421 AC: 890 AN: 2112

Alfa AF: 0.336 Hom.: 39790

Bravo AF: 0.442

Asia WGS AF: 0.444 AC: 1545 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	0.86
DANN	Benign	0.42
PhyloP100		-0.94
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: rs997917; hg19: chr8-54152378;