rs34709943

Variant names:

• chr8-53229274-T-A
• rs34709943
• ENST00000522508.1:n.*989A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-53229274-T-A
• chr8-53229274-T-C
• chr8-53229274-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000522508.1(OPRK1):​n.*989A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: OPRK1 ENST00000522508.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• Publications: 0 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]

LOC105375836 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*23A>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2	c.1166A>T	p.Tyr389Phe	missense_variant	Exon 4 of 4		NP_001305426.1
LOC105375836	NR_188096.1	n.1986T>A		non_coding_transcript_exon_variant	Exon 3 of 3
OPRK1	NM_001282904.2	c.*23A>T		3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*23A>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447284 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718002

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

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 44058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103806

Other (OTH) AF: 0.00 AC: 0 AN: 59738

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.9
DANN	Benign	0.79
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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: rs34709943; hg19: chr8-54141834;