8-53228229-C-T

Variant names:

• chr8-53228229-C-T
• rs16918853
• NM_000912.5:c.*1068G>A

Variant summary

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

The NM_000912.5(OPRK1):​c.*1068G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,126 control chromosomes in the GnomAD database, including 3,119 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 0.17 (3119 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 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.*1068G>A		3_prime_UTR	Exon 4 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.*981G>A		3_prime_UTR	Exon 4 of 4	NP_001305426.1	A0A5F9ZI09
	OPRK1	NM_001282904.2		c.*1068G>A		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.*1068G>A		3_prime_UTR	Exon 4 of 4	ENSP00000265572.3	P41145-1
	OPRK1	ENST00000673285.2		c.*981G>A		3_prime_UTR	Exon 4 of 4	ENSP00000500765.2	A0A5F9ZI09
	ENSG00000254687	ENST00000524425.1	TSL:3	n.670+11725C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26469 AN: 152008 Hom.: 3111 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0701

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.173

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.174 AC: 26515 AN: 152126 Hom.: 3119 Cov.: 32 AF XY: 0.174 AC XY: 12918 AN XY: 74388

African (AFR) AF: 0.327 AC: 13555 AN: 41462

American (AMR) AF: 0.231 AC: 3519 AN: 15258

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

East Asian (EAS) AF: 0.0699 AC: 362 AN: 5182

South Asian (SAS) AF: 0.105 AC: 504 AN: 4818

European-Finnish (FIN) AF: 0.0895 AC: 949 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0959 AC: 6520 AN: 68006

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.122 Hom.: 5618

Bravo AF: 0.193

Asia WGS AF: 0.106 AC: 368 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.57
PhyloP100		0.031
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: rs16918853; hg19: chr8-54140789; COSMIC: COSV105043399; COSMIC: COSV105043399;