rs7820807

Variant names:

• chr8-53226301-T-C
• rs7820807
• NM_000912.5:c.*2996A>G

Variant summary

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

The NM_000912.5(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 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 7 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]

ENSG00000254687 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.*2996A>G		3_prime_UTR	Exon 4 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.*2909A>G		3_prime_UTR	Exon 4 of 4	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.*2996A>G		3_prime_UTR	Exon 5 of 5	NP_001269833.1	P41145-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.*2996A>G		3_prime_UTR	Exon 4 of 4	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000673285.2		c.*2909A>G		3_prime_UTR	Exon 4 of 4	ENSP00000500765.2	A0A5F9ZI09
	ENSG00000254687	ENST00000524425.1	TSL:3	n.670+9797T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

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: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.348 AC: 14443 AN: 41452

American (AMR) AF: 0.231 AC: 3532 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3472

East Asian (EAS) AF: 0.0704 AC: 364 AN: 5172

South Asian (SAS) AF: 0.105 AC: 508 AN: 4828

European-Finnish (FIN) AF: 0.0890 AC: 944 AN: 10606

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.0958 AC: 6513 AN: 67996

Other (OTH) AF: 0.176 AC: 373 AN: 2114

Alfa AF: 0.147 Hom.: 785

Bravo AF: 0.199

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.76
PhyloP100		-0.75
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7820807;

hg19: chr8-54138861;