rs9282806

Positions:

• chr8-53251109-G-A

Variant summary

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

The ENST00000265572.8(OPRK1):​c.-48-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,417,366 control chromosomes in the GnomAD database, including 322 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.027 (191 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (131 hom.)
• Consequence: OPRK1 ENST00000265572.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59

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: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.-48-24C>T		intron_variant		ENST00000265572.8	NP_000903.2
OPRK1	NM_001282904.2	c.-489-24C>T		intron_variant			NP_001269833.1
OPRK1	NM_001318497.2	c.-48-24C>T		intron_variant			NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000520287.5	c.-72C>T		5_prime_UTR_variant	1/3	1		ENSP00000429706	P1
OPRK1	ENST00000265572.8	c.-48-24C>T		intron_variant		1	NM_000912.5	ENSP00000265572	P1
OPRK1	ENST00000522508.1	c.-48-24C>T		intron_variant, NMD_transcript_variant		1		ENSP00000428231
OPRK1	ENST00000673285.2	c.-48-24C>T		intron_variant				ENSP00000500765

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4092 AN: 152182 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000367

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00263 AC: 3322 AN: 1265066 Hom.: 131 Cov.: 31 AF XY: 0.00236 AC XY: 1446 AN XY: 613330

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.00561

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000329

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000256

Gnomad4 OTH exome AF: 0.00585

GnomAD4 genome AF: 0.0270 AC: 4107 AN: 152300 Hom.: 191 Cov.: 33 AF XY: 0.0259 AC XY: 1927 AN XY: 74458

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000367

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0231 Hom.: 25

Bravo AF: 0.0304

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.93
BranchPoint Hunter		3.0

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: rs9282806; hg19: chr8-54163669;