rs10958350

Variant names:

• chr8-53237506-G-A
• rs10958350
• NM_000912.5:c.258-2395C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-53237506-G-A
• chr8-53237506-G-T

Variant summary

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

The NM_000912.5(OPRK1):​c.258-2395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 152,232 control chromosomes in the GnomAD database, including 339 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 0.066 (339 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211
• Publications: 3 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]

ENSG00000254687 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.258-2395C>T		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.258-2395C>T		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-10-2395C>T		intron_variant	Intron 3 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.258-2395C>T		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes AF: 0.0656 AC: 9977 AN: 152114 Hom.: 333 Cov.: 33

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.0705

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0614

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0776

Gnomad OTH AF: 0.0742

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

GnomAD4 genome AF: 0.0656 AC: 9990 AN: 152232 Hom.: 339 Cov.: 33 AF XY: 0.0658 AC XY: 4896 AN XY: 74434

African (AFR) AF: 0.0498 AC: 2067 AN: 41546

American (AMR) AF: 0.0539 AC: 825 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3470

East Asian (EAS) AF: 0.0705 AC: 365 AN: 5178

South Asian (SAS) AF: 0.0538 AC: 259 AN: 4818

European-Finnish (FIN) AF: 0.0614 AC: 650 AN: 10590

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0776 AC: 5279 AN: 68020

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0371 Hom.: 23

Bravo AF: 0.0643

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		0.21
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: rs10958350; hg19: chr8-54150066;