chr8-53228644-G-A

Variant names:

• chr8-53228644-G-A
• rs3802282
• NM_000912.5:c.*653C>T

Variant summary

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

The NM_000912.5(OPRK1):​c.*653C>T 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 152,126 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 (6225 hom., cov: 33)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 6 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]

LOC105375836 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.*653C>T		3_prime_UTR	Exon 4 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.*566C>T		3_prime_UTR	Exon 4 of 4	NP_001305426.1
	OPRK1	NM_001282904.2		c.*653C>T		3_prime_UTR	Exon 5 of 5	NP_001269833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.*653C>T		3_prime_UTR	Exon 4 of 4	ENSP00000265572.3
	OPRK1	ENST00000673285.2		c.*566C>T		3_prime_UTR	Exon 4 of 4	ENSP00000500765.2
	ENSG00000254687	ENST00000524425.1	TSL:3	n.670+12140G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36924 AN: 151994 Hom.: 6213 Cov.: 33

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 1 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.243 AC: 36985 AN: 152112 Hom.: 6225 Cov.: 33 AF XY: 0.240 AC XY: 17853 AN XY: 74374

African (AFR) AF: 0.476 AC: 19738 AN: 41472

American (AMR) AF: 0.265 AC: 4055 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 366 AN: 5182

South Asian (SAS) AF: 0.137 AC: 662 AN: 4816

European-Finnish (FIN) AF: 0.109 AC: 1151 AN: 10580

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9680 AN: 67998

Other (OTH) AF: 0.230 AC: 485 AN: 2108

Alfa AF: 0.199 Hom.: 1327

Bravo AF: 0.265

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.9
DANN	Benign	0.35
PhyloP100		1.4
Mutation Taster		=100/0	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: rs3802282; hg19: chr8-54141204;