rs16918941

Variant names:

• chr8-53248142-A-G
• rs16918941
• NM_000912.5:c.257+2639T>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.257+2639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 152,182 control chromosomes in the GnomAD database, including 386 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 0.070 (386 hom., cov: 31)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+2639T>C		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.257+2639T>C		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-185+2639T>C		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+2639T>C		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000520287.5	c.257+2639T>C		intron_variant	Intron 1 of 2	1		ENSP00000429706.1
OPRK1	ENST00000522508.1	n.257+2639T>C		intron_variant	Intron 2 of 4	1		ENSP00000428231.1
OPRK1	ENST00000673285.2	c.257+2639T>C		intron_variant	Intron 2 of 3			ENSP00000500765.2

Frequencies

GnomAD3 genomes AF: 0.0705 AC: 10716 AN: 152066 Hom.: 383 Cov.: 31

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0808

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.0531

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0757

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

GnomAD4 genome AF: 0.0704 AC: 10718 AN: 152182 Hom.: 386 Cov.: 31 AF XY: 0.0705 AC XY: 5244 AN XY: 74396

African (AFR) AF: 0.0660 AC: 2742 AN: 41538

American (AMR) AF: 0.0551 AC: 842 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0808 AC: 280 AN: 3466

East Asian (EAS) AF: 0.0759 AC: 393 AN: 5180

South Asian (SAS) AF: 0.0527 AC: 254 AN: 4818

European-Finnish (FIN) AF: 0.0615 AC: 651 AN: 10578

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0778 AC: 5288 AN: 68012

Other (OTH) AF: 0.0759 AC: 160 AN: 2108

Alfa AF: 0.0755 Hom.: 731

Bravo AF: 0.0699

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.56
PhyloP100		0.39
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: rs16918941; hg19: chr8-54160702;