chr8-53251335-C-T

Position:

• chr8-53251335-C-T

Variant summary

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

The ENST00000520287.5(OPRK1):​c.-298G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 460,126 control chromosomes in the GnomAD database, including 472 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 0.044 (168 hom., cov: 32)
  • Exomes 𝑓: 0.040 (304 hom.)
• Consequence: OPRK1 ENST00000520287.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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

Verdict is Benign. Variant got -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 = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.-49+113G>A		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-490+113G>A		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.-49+113G>A		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000520287.5	c.-298G>A		5_prime_UTR_variant	1/3	1		ENSP00000429706	P1
OPRK1	ENST00000265572.8	c.-49+113G>A		intron_variant		1	NM_000912.5	ENSP00000265572	P1
OPRK1	ENST00000522508.1	c.-49+113G>A		intron_variant, NMD_transcript_variant		1		ENSP00000428231
OPRK1	ENST00000673285.2	c.-49+113G>A		intron_variant				ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.0437 AC: 6647 AN: 152112 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0628

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.0186

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0455

Gnomad OTH AF: 0.0382

GnomAD4 exome AF: 0.0397 AC: 12221 AN: 307896 Hom.: 304 Cov.: 3 AF XY: 0.0395 AC XY: 6346 AN XY: 160486

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.0193

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.0000518

Gnomad4 SAS exome AF: 0.0398

Gnomad4 FIN exome AF: 0.0241

Gnomad4 NFE exome AF: 0.0466

Gnomad4 OTH exome AF: 0.0410

GnomAD4 genome AF: 0.0437 AC: 6648 AN: 152230 Hom.: 168 Cov.: 32 AF XY: 0.0417 AC XY: 3101 AN XY: 74422

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.0329

Gnomad4 FIN AF: 0.0186

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0178 Hom.: 9

Bravo AF: 0.0447

Asia WGS AF: 0.0210 AC: 75 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.78
DANN	Benign	0.80

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: rs16918955; hg19: chr8-54163895; COSMIC: COSV55570538; COSMIC: COSV55570538;