8-53230255-G-T

Variant names:

• chr8-53230255-G-T
• rs7817710
• NM_000912.5:c.611-426C>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.611-426C>A 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 151,968 control chromosomes in the GnomAD database, including 2,946 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 (2946 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 9 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.

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.611-426C>A		intron	N/A	NP_000903.2
	OPRK1	NM_001318497.2		c.611-426C>A		intron	N/A	NP_001305426.1
	OPRK1	NM_001282904.2		c.344-426C>A		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.611-426C>A		intron	N/A	ENSP00000265572.3
	OPRK1	ENST00000520287.5	TSL:1	c.611-426C>A		intron	N/A	ENSP00000429706.1
	OPRK1	ENST00000524278.5	TSL:1	c.344-426C>A		intron	N/A	ENSP00000430923.1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25142 AN: 151850 Hom.: 2935 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0828

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: 25190 AN: 151968 Hom.: 2946 Cov.: 32 AF XY: 0.166 AC XY: 12299 AN XY: 74292

African (AFR) AF: 0.324 AC: 13419 AN: 41394

American (AMR) AF: 0.223 AC: 3407 AN: 15256

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

East Asian (EAS) AF: 0.0680 AC: 352 AN: 5180

South Asian (SAS) AF: 0.0871 AC: 419 AN: 4808

European-Finnish (FIN) AF: 0.0875 AC: 925 AN: 10574

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

European-Non Finnish (NFE) AF: 0.0828 AC: 5630 AN: 67970

Other (OTH) AF: 0.168 AC: 355 AN: 2114

Alfa AF: 0.109 Hom.: 2168

Bravo AF: 0.183

Asia WGS AF: 0.0980 AC: 340 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.092
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: rs7817710; hg19: chr8-54142815;