NM_000912.5:c.258-5120A>G

Variant names:

• chr8-53240231-T-C
• rs1365097
• NM_000912.5:c.258-5120A>G

Variant summary

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

The NM_000912.5(OPRK1):​c.258-5120A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,004 control chromosomes in the GnomAD database, including 16,738 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 0.43 (16738 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-5120A>G		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.258-5120A>G		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-11+2508A>G		intron_variant	Intron 3 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-5120A>G		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65458 AN: 151886 Hom.: 16686 Cov.: 32

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.424

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.431 AC: 65568 AN: 152004 Hom.: 16738 Cov.: 32 AF XY: 0.432 AC XY: 32108 AN XY: 74314

African (AFR) AF: 0.720 AC: 29857 AN: 41462

American (AMR) AF: 0.386 AC: 5894 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1883 AN: 5180

South Asian (SAS) AF: 0.445 AC: 2139 AN: 4806

European-Finnish (FIN) AF: 0.289 AC: 3054 AN: 10556

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19805 AN: 67950

Other (OTH) AF: 0.427 AC: 901 AN: 2110

Alfa AF: 0.374 Hom.: 2095

Bravo AF: 0.448

Asia WGS AF: 0.445 AC: 1547 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		-0.078
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: rs1365097; hg19: chr8-54152791;