8-53226058-G-T

Position:

• chr8-53226058-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.*3239C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,000 control chromosomes in the GnomAD database, including 6,285 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 0.24 (6285 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*3239C>A		3_prime_UTR_variant	4/4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.*3152C>A		3_prime_UTR_variant	4/4		NP_001305426.1
OPRK1	NM_001282904.2	c.*3239C>A		3_prime_UTR_variant	5/5		NP_001269833.1
LOC105375836	NR_188096.1	n.640-1870G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*3239C>A		3_prime_UTR_variant	4/4	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000673285.2	c.*3152C>A		3_prime_UTR_variant	4/4			ENSP00000500765.2
ENSG00000254687	ENST00000524425.1	n.670+9554G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36980 AN: 151880 Hom.: 6274 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

GnomAD4 genome AF: 0.244 AC: 37044 AN: 151998 Hom.: 6285 Cov.: 32 AF XY: 0.240 AC XY: 17855 AN XY: 74304

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.228

Alfa AF: 0.158 Hom.: 1980

Bravo AF: 0.267

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs7832417; hg19: chr8-54138618;