8-53234910-G-A

Variant names:

• chr8-53234910-G-A
• rs7815824
• NM_000912.5:c.459C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000912.5(OPRK1):​c.459C>T​(p.Ser153Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,614,024 control chromosomes in the GnomAD database, including 1,818 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 0.068 (605 hom., cov: 32)
  • Exomes 𝑓: 0.033 (1213 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.822
• Publications: 12 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.822 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.459C>T	p.Ser153Ser	synonymous	Exon 3 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.459C>T	p.Ser153Ser	synonymous	Exon 3 of 4	NP_001305426.1
	OPRK1	NM_001282904.2		c.192C>T	p.Ser64Ser	synonymous	Exon 4 of 5	NP_001269833.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.459C>T	p.Ser153Ser	synonymous	Exon 3 of 4	ENSP00000265572.3
	OPRK1	ENST00000520287.5	TSL:1	c.459C>T	p.Ser153Ser	synonymous	Exon 2 of 3	ENSP00000429706.1
	OPRK1	ENST00000524278.5	TSL:1	c.192C>T	p.Ser64Ser	synonymous	Exon 2 of 3	ENSP00000430923.1

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10333 AN: 152024 Hom.: 605 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.00809

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0593

GnomAD2 exomes AF: 0.0368 AC: 9253 AN: 251400 AF XY: 0.0339

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.0524

Gnomad EAS exome AF: 0.0173

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0301

Gnomad OTH exome AF: 0.0346

GnomAD4 exome AF: 0.0326 AC: 47670 AN: 1461882 Hom.: 1213 Cov.: 31 AF XY: 0.0315 AC XY: 22887 AN XY: 727242

African (AFR) AF: 0.173 AC: 5803 AN: 33480

American (AMR) AF: 0.0230 AC: 1028 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 1488 AN: 26136

East Asian (EAS) AF: 0.0156 AC: 620 AN: 39700

South Asian (SAS) AF: 0.0102 AC: 883 AN: 86258

European-Finnish (FIN) AF: 0.0485 AC: 2589 AN: 53418

Middle Eastern (MID) AF: 0.0253 AC: 146 AN: 5768

European-Non Finnish (NFE) AF: 0.0295 AC: 32855 AN: 1112004

Other (OTH) AF: 0.0374 AC: 2258 AN: 60394

GnomAD4 genome AF: 0.0680 AC: 10352 AN: 152142 Hom.: 605 Cov.: 32 AF XY: 0.0664 AC XY: 4944 AN XY: 74404

African (AFR) AF: 0.162 AC: 6717 AN: 41450

American (AMR) AF: 0.0377 AC: 577 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3468

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5182

South Asian (SAS) AF: 0.00810 AC: 39 AN: 4816

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10592

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2087 AN: 68016

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0521 Hom.: 185

Bravo AF: 0.0724

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.0321

EpiControl AF: 0.0301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.9
DANN	Benign	0.86
PhyloP100		0.82
Mutation Taster		=96/4	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: rs7815824; hg19: chr8-54147470; COSMIC: COSV55571018;