8-53228603-T-C

Position:

• chr8-53228603-T-C

Variant summary

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

The ENST00000265572.8(OPRK1):​c.*694A>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 0.243 in 152,232 control chromosomes in the GnomAD database, including 6,225 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 (6224 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: OPRK1 ENST00000265572.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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]

LOC105375836 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*694A>G		3_prime_UTR_variant	4/4	ENST00000265572.8	NP_000903.2
LOC105375836	XR_928877.2	n.1315T>C		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001282904.2	c.*694A>G		3_prime_UTR_variant	5/5		NP_001269833.1
OPRK1	NM_001318497.2	c.*607A>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.*694A>G		3_prime_UTR_variant	4/4	1	NM_000912.5	ENSP00000265572	P1
	ENST00000524425.1	n.670+12099T>C		intron_variant, non_coding_transcript_variant		3
OPRK1	ENST00000673285.2	c.*607A>G		3_prime_UTR_variant	4/4			ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36924 AN: 152100 Hom.: 6212 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.143 AC: 2 AN: 14 Hom.: 1 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.243 AC: 36985 AN: 152218 Hom.: 6224 Cov.: 32 AF XY: 0.240 AC XY: 17858 AN XY: 74444

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0705

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.230

Alfa AF: 0.161 Hom.: 3685

Bravo AF: 0.265

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.98
DANN	Benign	0.71

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: rs3802281; hg19: chr8-54141163;