rs1051660

Variant names:

• chr8-53251002-C-A
• rs1051660
• NM_000912.5:c.36G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-53251002-C-A
• chr8-53251002-C-G
• chr8-53251002-C-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.36G>T​(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 1,574,264 control chromosomes in the GnomAD database, including 8,124 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 0.094 (754 hom., cov: 33)
  • Exomes 𝑓: 0.098 (7370 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 61 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.36G>T	p.Pro12Pro	synonymous_variant	Exon 2 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-406G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 5		NP_001269833.1
OPRK1	NM_001318497.2	c.36G>T	p.Pro12Pro	synonymous_variant	Exon 2 of 4		NP_001305426.1
OPRK1	NM_001282904.2	c.-406G>T		5_prime_UTR_variant	Exon 2 of 5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.36G>T	p.Pro12Pro	synonymous_variant	Exon 2 of 4	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000520287.5	c.36G>T	p.Pro12Pro	synonymous_variant	Exon 1 of 3	1		ENSP00000429706.1
OPRK1	ENST00000522508.1	n.36G>T		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000428231.1
OPRK1	ENST00000673285.2	c.36G>T	p.Pro12Pro	synonymous_variant	Exon 2 of 4			ENSP00000500765.2

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14357 AN: 152126 Hom.: 753 Cov.: 33

Gnomad AFR AF: 0.0990

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0561

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0899

GnomAD2 exomes AF: 0.113 AC: 20400 AN: 180668 AF XY: 0.120

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0488

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.0963

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.0975 AC: 138684 AN: 1422020 Hom.: 7370 Cov.: 32 AF XY: 0.100 AC XY: 70708 AN XY: 703986

African (AFR) AF: 0.0964 AC: 3123 AN: 32382

American (AMR) AF: 0.0490 AC: 1915 AN: 39082

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 2729 AN: 24088

East Asian (EAS) AF: 0.165 AC: 6390 AN: 38680

South Asian (SAS) AF: 0.181 AC: 14473 AN: 80112

European-Finnish (FIN) AF: 0.108 AC: 5242 AN: 48434

Middle Eastern (MID) AF: 0.106 AC: 589 AN: 5566

European-Non Finnish (NFE) AF: 0.0896 AC: 98071 AN: 1094852

Other (OTH) AF: 0.105 AC: 6152 AN: 58824

GnomAD4 genome AF: 0.0943 AC: 14360 AN: 152244 Hom.: 754 Cov.: 33 AF XY: 0.0967 AC XY: 7199 AN XY: 74430

African (AFR) AF: 0.0989 AC: 4110 AN: 41564

American (AMR) AF: 0.0560 AC: 857 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3470

East Asian (EAS) AF: 0.167 AC: 861 AN: 5148

South Asian (SAS) AF: 0.179 AC: 865 AN: 4822

European-Finnish (FIN) AF: 0.101 AC: 1075 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0877 AC: 5962 AN: 68002

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0400 Hom.: 140

Bravo AF: 0.0895

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.8
DANN	Benign	0.87
PhyloP100		-0.17
PromoterAI		-0.013	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1051660; hg19: chr8-54163562; COSMIC: COSV55569026;