chr8-53240123-C-A

Position:

• chr8-53240123-C-A

Variant summary

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

The NM_000912.5(OPRK1):​c.258-5012G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,920 control chromosomes in the GnomAD database, including 16,152 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 (16152 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-5012G>T		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-11+2616G>T		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.258-5012G>T		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-5012G>T		intron_variant		1	NM_000912.5	ENSP00000265572	P1
	ENST00000524425.1	n.671-2405C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64551 AN: 151802 Hom.: 16101 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.426 AC: 64659 AN: 151920 Hom.: 16152 Cov.: 32 AF XY: 0.426 AC XY: 31657 AN XY: 74236

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.364

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.422

Alfa AF: 0.372 Hom.: 1550

Bravo AF: 0.441

Asia WGS AF: 0.439 AC: 1525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.32

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: rs1365098; hg19: chr8-54152683;