8-53240545-C-T

Variant names:

• chr8-53240545-C-T
• rs6473798
• NM_000912.5:c.258-5434G>A

Variant summary

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

The NM_000912.5(OPRK1):​c.258-5434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,898 control chromosomes in the GnomAD database, including 13,247 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 0.38 (13247 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-5434G>A		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.258-5434G>A		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-11+2194G>A		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.258-5434G>A		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57904 AN: 151780 Hom.: 13197 Cov.: 32

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.382 AC: 58014 AN: 151898 Hom.: 13247 Cov.: 32 AF XY: 0.385 AC XY: 28556 AN XY: 74212

African (AFR) AF: 0.639 AC: 26465 AN: 41410

American (AMR) AF: 0.357 AC: 5454 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1872 AN: 5156

South Asian (SAS) AF: 0.410 AC: 1968 AN: 4798

European-Finnish (FIN) AF: 0.269 AC: 2833 AN: 10528

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16685 AN: 67960

Other (OTH) AF: 0.384 AC: 807 AN: 2104

Alfa AF: 0.292 Hom.: 12172

Bravo AF: 0.397

Asia WGS AF: 0.421 AC: 1464 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.41
PhyloP100		-0.32
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: rs6473798; hg19: chr8-54153105;