8-53226058-G-T

Variant names:

• chr8-53226058-G-T
• rs7832417
• NM_000912.5:c.*3239C>A

Variant summary

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

The NM_000912.5(OPRK1):​c.*3239C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,000 control chromosomes in the GnomAD database, including 6,285 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 0.24 (6285 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*3239C>A		3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.*3152C>A		3_prime_UTR_variant	Exon 4 of 4		NP_001305426.1
OPRK1	NM_001282904.2	c.*3239C>A		3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1
LOC105375836	NR_188096.1	n.640-1870G>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*3239C>A		3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000673285.2	c.*3152C>A		3_prime_UTR_variant	Exon 4 of 4			ENSP00000500765.2
ENSG00000254687	ENST00000524425.1	n.670+9554G>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36980 AN: 151880 Hom.: 6274 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.244 AC: 37044 AN: 151998 Hom.: 6285 Cov.: 32 AF XY: 0.240 AC XY: 17855 AN XY: 74304

African (AFR) AF: 0.479 AC: 19852 AN: 41416

American (AMR) AF: 0.265 AC: 4053 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 667 AN: 3466

East Asian (EAS) AF: 0.0704 AC: 363 AN: 5154

South Asian (SAS) AF: 0.138 AC: 667 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10564

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9659 AN: 67986

Other (OTH) AF: 0.228 AC: 482 AN: 2110

Alfa AF: 0.164 Hom.: 2503

Bravo AF: 0.267

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.38
PhyloP100		-0.32
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: rs7832417; hg19: chr8-54138618;