chr8-53248556-T-C

Variant names:

• chr8-53248556-T-C
• rs6985606
• NM_000912.5:c.257+2225A>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.257+2225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 152,104 control chromosomes in the GnomAD database, including 32,750 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 0.63 (32750 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 19 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.257+2225A>G		intron	N/A	NP_000903.2
	OPRK1	NM_001318497.2		c.257+2225A>G		intron	N/A	NP_001305426.1
	OPRK1	NM_001282904.2		c.-185+2225A>G		intron	N/A	NP_001269833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.257+2225A>G		intron	N/A	ENSP00000265572.3
	OPRK1	ENST00000520287.5	TSL:1	c.257+2225A>G		intron	N/A	ENSP00000429706.1
	OPRK1	ENST00000522508.1	TSL:1	n.257+2225A>G		intron	N/A	ENSP00000428231.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95898 AN: 151988 Hom.: 32688 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.631 AC: 96020 AN: 152104 Hom.: 32750 Cov.: 32 AF XY: 0.632 AC XY: 46987 AN XY: 74330

African (AFR) AF: 0.908 AC: 37692 AN: 41520

American (AMR) AF: 0.626 AC: 9558 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2218 AN: 3466

East Asian (EAS) AF: 0.590 AC: 3053 AN: 5172

South Asian (SAS) AF: 0.604 AC: 2912 AN: 4824

European-Finnish (FIN) AF: 0.477 AC: 5040 AN: 10560

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33688 AN: 67972

Other (OTH) AF: 0.629 AC: 1329 AN: 2114

Alfa AF: 0.545 Hom.: 38768

Bravo AF: 0.653

Asia WGS AF: 0.628 AC: 2186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.46
PhyloP100		-3.2
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: rs6985606; hg19: chr8-54161116;