rs35160174

Variant names:

• chr8-53228623-GAAAA-G
• rs35160174
• NM_000912.5:c.*670_*673delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr8-53228623-GAAAA-G
• chr8-53228623-GAAAA-GAAA
• chr8-53228623-GAAAA-GAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000912.5(OPRK1):​c.*670_*673delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,836 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000020 (0 hom., cov: 33)
• Consequence: OPRK1 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.22
• 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]

LOC105375836 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000912.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.*670_*673delTTTT		3_prime_UTR	Exon 4 of 4	NP_000903.2
	OPRK1	NM_001318497.2		c.*583_*586delTTTT		3_prime_UTR	Exon 4 of 4	NP_001305426.1
	OPRK1	NM_001282904.2		c.*670_*673delTTTT		3_prime_UTR	Exon 5 of 5	NP_001269833.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.*670_*673delTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000265572.3
	OPRK1	ENST00000673285.2		c.*583_*586delTTTT		3_prime_UTR	Exon 4 of 4	ENSP00000500765.2
	ENSG00000254687	ENST00000524425.1	TSL:3	n.670+12124_670+12127delAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151836 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

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

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151836 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74130

African (AFR) AF: 0.0000484 AC: 2 AN: 41352

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67916

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2

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: rs35160174; hg19: chr8-54141183;