rs2303432

Variant names:

• chr8-53244657-G-A
• rs2303432
• NM_000912.5:c.257+6124C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-53244657-G-A
• chr8-53244657-G-C

Variant summary

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

The NM_000912.5(OPRK1):​c.257+6124C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 152,200 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: -0.153
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+6124C>T		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.257+6124C>T		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-184-1745C>T		intron_variant	Intron 2 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.257+6124C>T		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000520287.5	c.257+6124C>T		intron_variant	Intron 1 of 2	1		ENSP00000429706.1
OPRK1	ENST00000522508.1	n.258-1745C>T		intron_variant	Intron 2 of 4	1		ENSP00000428231.1
OPRK1	ENST00000673285.2	c.257+6124C>T		intron_variant	Intron 2 of 3			ENSP00000500765.2

Frequencies

GnomAD3 genomes AF: 0.0998 AC: 15184 AN: 152082 Hom.: 833 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0589

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0880

Gnomad OTH AF: 0.0951

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

GnomAD4 genome AF: 0.0998 AC: 15186 AN: 152200 Hom.: 834 Cov.: 33 AF XY: 0.102 AC XY: 7596 AN XY: 74420

African (AFR) AF: 0.117 AC: 4845 AN: 41526

American (AMR) AF: 0.0587 AC: 898 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3470

East Asian (EAS) AF: 0.167 AC: 865 AN: 5180

South Asian (SAS) AF: 0.180 AC: 870 AN: 4830

European-Finnish (FIN) AF: 0.103 AC: 1085 AN: 10578

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0880 AC: 5983 AN: 67998

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0860 Hom.: 822

Bravo AF: 0.0956

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.82
DANN	Benign	0.29
PhyloP100		-0.15
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: rs2303432; hg19: chr8-54157217;