8-53242895-T-G

Variant names:

• chr8-53242895-T-G
• rs12548098
• ENST00000522508.1:n.275A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000912.5(OPRK1):​c.258-7784A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000176 in 1,135,474 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000018 (0 hom.)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-7784A>C		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-167A>C		5_prime_UTR_variant	Exon 3 of 5		NP_001269833.1
OPRK1	NM_001318497.2	c.258-7784A>C		intron_variant	Intron 2 of 3		NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-7784A>C		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000176 AC: 2 AN: 1135474 Hom.: 0 Cov.: 31 AF XY: 0.00000180 AC XY: 1 AN XY: 556810

African (AFR) AF: 0.00 AC: 0 AN: 24364

American (AMR) AF: 0.00 AC: 0 AN: 28228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15902

East Asian (EAS) AF: 0.00 AC: 0 AN: 12752

South Asian (SAS) AF: 0.00 AC: 0 AN: 76024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4396

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 919760

Other (OTH) AF: 0.00 AC: 0 AN: 41460

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.65
PhyloP100		-0.19

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: rs12548098; hg19: chr8-54155455;