rs7820807

Positions:

• chr8-53226301-T-C

Variant summary

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

The ENST00000265572.8(OPRK1):​c.*2996A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,108 control chromosomes in the GnomAD database, including 3,420 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 0.18 (3420 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: OPRK1 ENST00000265572.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*2996A>G		3_prime_UTR_variant	4/4	ENST00000265572.8	NP_000903.2
LOC105375836	XR_928877.2	n.640-1627T>C		intron_variant, non_coding_transcript_variant
OPRK1	NM_001282904.2	c.*2996A>G		3_prime_UTR_variant	5/5		NP_001269833.1
OPRK1	NM_001318497.2	c.*2909A>G		3_prime_UTR_variant	4/4		NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*2996A>G		3_prime_UTR_variant	4/4	1	NM_000912.5	ENSP00000265572	P1
	ENST00000524425.1	n.670+9797T>C		intron_variant, non_coding_transcript_variant		3
OPRK1	ENST00000673285.2	c.*2909A>G		3_prime_UTR_variant	4/4			ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27358 AN: 151986 Hom.: 3408 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0706

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.180 AC: 27418 AN: 152104 Hom.: 3420 Cov.: 32 AF XY: 0.179 AC XY: 13307 AN XY: 74374

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.231

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.0958

Gnomad4 OTH AF: 0.176

Alfa AF: 0.138 Hom.: 648

Bravo AF: 0.199

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.76

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: rs7820807; hg19: chr8-54138861;