chr8-53240422-T-C

Position:

• chr8-53240422-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000912.5(OPRK1):​c.258-5311A>G 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 152,064 control chromosomes in the GnomAD database, including 13,273 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 (13273 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-5311A>G		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-11+2317A>G		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.258-5311A>G		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-5311A>G		intron_variant		1	NM_000912.5	ENSP00000265572	P1
	ENST00000524425.1	n.671-2106T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57988 AN: 151946 Hom.: 13223 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.382 AC: 58097 AN: 152064 Hom.: 13273 Cov.: 33 AF XY: 0.385 AC XY: 28617 AN XY: 74336

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.384

Alfa AF: 0.329 Hom.: 1240

Bravo AF: 0.397

Asia WGS AF: 0.423 AC: 1471 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	0.85
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs6473797; hg19: chr8-54152982;