chr8-53250326-G-A

Variant names:

• chr8-53250326-G-A
• rs12056414
• NM_000912.5:c.257+455C>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.257+455C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 152,128 control chromosomes in the GnomAD database, including 753 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 0.094 (753 hom., cov: 32)
• Consequence: OPRK1 NM_000912.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• 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 rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.257+455C>T		intron_variant	Intron 2 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.257+455C>T		intron_variant	Intron 2 of 3		NP_001305426.1
OPRK1	NM_001282904.2	c.-185+455C>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+455C>T		intron_variant	Intron 2 of 3	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000520287.5	c.257+455C>T		intron_variant	Intron 1 of 2	1		ENSP00000429706.1
OPRK1	ENST00000522508.1	n.257+455C>T		intron_variant	Intron 2 of 4	1		ENSP00000428231.1
OPRK1	ENST00000673285.2	c.257+455C>T		intron_variant	Intron 2 of 3			ENSP00000500765.2

Frequencies

GnomAD3 genomes AF: 0.0945 AC: 14362 AN: 152010 Hom.: 752 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0562

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0877

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0944 AC: 14365 AN: 152128 Hom.: 753 Cov.: 32 AF XY: 0.0969 AC XY: 7210 AN XY: 74372

African (AFR) AF: 0.0990 AC: 4108 AN: 41492

American (AMR) AF: 0.0561 AC: 857 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3462

East Asian (EAS) AF: 0.167 AC: 862 AN: 5174

South Asian (SAS) AF: 0.179 AC: 862 AN: 4808

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0877 AC: 5967 AN: 68004

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0957 Hom.: 384

Bravo AF: 0.0895

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.25
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: rs12056414; hg19: chr8-54162886;