8-53251002-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000912.5(OPRK1):​c.36G>C​(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.169 with no splicing effect.

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.36G>C	p.Pro12Pro	synonymous	Exon 2 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 4	NP_001305426.1
	OPRK1	NM_001282904.2		c.-406G>C		5_prime_UTR	Exon 2 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.36G>C	p.Pro12Pro	synonymous	Exon 2 of 4	ENSP00000265572.3
	OPRK1	ENST00000520287.5	TSL:1	c.36G>C	p.Pro12Pro	synonymous	Exon 1 of 3	ENSP00000429706.1
	OPRK1	ENST00000522508.1	TSL:1	n.36G>C		non_coding_transcript_exon	Exon 2 of 5	ENSP00000428231.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422122 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 704048

African (AFR) AF: 0.00 AC: 0 AN: 32382

American (AMR) AF: 0.00 AC: 0 AN: 39088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24088

East Asian (EAS) AF: 0.00 AC: 0 AN: 38688

South Asian (SAS) AF: 0.00 AC: 0 AN: 80132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5568

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094902

Other (OTH) AF: 0.00 AC: 0 AN: 58828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.3
DANN	Benign	0.73
PhyloP100		-0.17
PromoterAI		-0.025	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;