rs7016778

Variant names:

• chr8-53237545-A-T
• rs7016778
• NM_000912.5:c.258-2434T>A

Variant summary

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

The NM_000912.5(OPRK1):​c.258-2434T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,082 control chromosomes in the GnomAD database, including 2,855 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 (2855 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.974
• Publications: 12 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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.258-2434T>A		intron	N/A	NP_000903.2
	OPRK1	NM_001318497.2		c.258-2434T>A		intron	N/A	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.-10-2434T>A		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.258-2434T>A		intron	N/A	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000520287.5	TSL:1	c.258-2434T>A		intron	N/A	ENSP00000429706.1	P41145-1
	OPRK1	ENST00000524278.5	TSL:1	c.-11+973T>A		intron	N/A	ENSP00000430923.1	P41145-2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25702 AN: 151964 Hom.: 2840 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0710

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0799

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.169 AC: 25736 AN: 152082 Hom.: 2855 Cov.: 32 AF XY: 0.166 AC XY: 12318 AN XY: 74342

African (AFR) AF: 0.320 AC: 13266 AN: 41446

American (AMR) AF: 0.102 AC: 1567 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3466

East Asian (EAS) AF: 0.0710 AC: 367 AN: 5168

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4820

European-Finnish (FIN) AF: 0.0799 AC: 846 AN: 10584

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8430 AN: 67992

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.150 Hom.: 283

Bravo AF: 0.177

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.47
DANN	Benign	0.51
PhyloP100		-0.97
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: rs7016778; hg19: chr8-54150105;