8-53230988-C-G

Variant names:

• chr8-53230988-C-G
• rs16918884
• NM_000912.5:c.611-1159G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.611-1159G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,974 control chromosomes in the GnomAD database, including 2,948 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 0.17 (2948 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.611-1159G>C		intron_variant	Intron 3 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.611-1159G>C		intron_variant	Intron 3 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.344-1159G>C		intron_variant	Intron 4 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.611-1159G>C		intron_variant	Intron 3 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25214 AN: 151856 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.166 AC: 25261 AN: 151974 Hom.: 2948 Cov.: 32 AF XY: 0.166 AC XY: 12335 AN XY: 74266

African (AFR) AF: 0.325 AC: 13445 AN: 41414

American (AMR) AF: 0.224 AC: 3424 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 597 AN: 3468

East Asian (EAS) AF: 0.0704 AC: 364 AN: 5172

South Asian (SAS) AF: 0.0889 AC: 427 AN: 4802

European-Finnish (FIN) AF: 0.0878 AC: 926 AN: 10548

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0829 AC: 5637 AN: 67982

Other (OTH) AF: 0.168 AC: 355 AN: 2110

Alfa AF: 0.118 Hom.: 202

Bravo AF: 0.184

Asia WGS AF: 0.101 AC: 351 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.57
PhyloP100		0.0050
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: rs16918884; hg19: chr8-54143548;