rs9282806

Variant names:

• chr8-53251109-G-A
• rs9282806
• ENST00000520287.5:c.-72C>T

Variant summary

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

The ENST00000520287.5(OPRK1):​c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,417,366 control chromosomes in the GnomAD database, including 322 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 0.027 (191 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (131 hom.)
• Consequence: OPRK1 ENST00000520287.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520287.5. 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.-48-24C>T		intron	N/A	NP_000903.2
	OPRK1	NM_001318497.2		c.-48-24C>T		intron	N/A	NP_001305426.1
	OPRK1	NM_001282904.2		c.-489-24C>T		intron	N/A	NP_001269833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000520287.5	TSL:1	c.-72C>T		5_prime_UTR	Exon 1 of 3	ENSP00000429706.1
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.-48-24C>T		intron	N/A	ENSP00000265572.3
	OPRK1	ENST00000522508.1	TSL:1	n.-48-24C>T		intron	N/A	ENSP00000428231.1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4092 AN: 152182 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00263 AC: 3322 AN: 1265066 Hom.: 131 Cov.: 31 AF XY: 0.00236 AC XY: 1446 AN XY: 613330

African (AFR) AF: 0.102 AC: 2605 AN: 25474

American (AMR) AF: 0.00561 AC: 97 AN: 17294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17880

East Asian (EAS) AF: 0.00 AC: 0 AN: 31694

South Asian (SAS) AF: 0.000329 AC: 20 AN: 60812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30838

Middle Eastern (MID) AF: 0.00768 AC: 30 AN: 3906

European-Non Finnish (NFE) AF: 0.000256 AC: 262 AN: 1024552

Other (OTH) AF: 0.00585 AC: 308 AN: 52616

GnomAD4 genome AF: 0.0270 AC: 4107 AN: 152300 Hom.: 191 Cov.: 33 AF XY: 0.0259 AC XY: 1927 AN XY: 74458

African (AFR) AF: 0.0936 AC: 3889 AN: 41570

American (AMR) AF: 0.00908 AC: 139 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.000367 AC: 25 AN: 68028

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0256 Hom.: 28

Bravo AF: 0.0304

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		1.6
BranchPoint Hunter		3.0
PromoterAI		-0.00060	Neutral
Mutation Taster		=300/0	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: rs9282806; hg19: chr8-54163669;