chr8-53243717-T-C

Position:

• chr8-53243717-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.257+7064A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 152,278 control chromosomes in the GnomAD database, including 834 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 0.10 (834 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+7064A>G		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-184-805A>G		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.257+7064A>G		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.257+7064A>G		intron_variant		1	NM_000912.5	ENSP00000265572	P1
OPRK1	ENST00000520287.5	c.257+7064A>G		intron_variant		1		ENSP00000429706	P1
OPRK1	ENST00000522508.1	c.258-805A>G		intron_variant, NMD_transcript_variant		1		ENSP00000428231
OPRK1	ENST00000673285.2	c.257+7064A>G		intron_variant				ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15208 AN: 152160 Hom.: 833 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0999 AC: 15210 AN: 152278 Hom.: 834 Cov.: 33 AF XY: 0.102 AC XY: 7601 AN XY: 74452

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0588

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0880

Gnomad4 OTH AF: 0.0934

Alfa AF: 0.101 Hom.: 79

Bravo AF: 0.0958

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.015
DANN	Benign	0.77

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: rs7843965; hg19: chr8-54156277;