rs35373196

Variant names:

• chr8-53228986-G-A
• rs35373196
• ENST00000522508.1:n.*1277C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-53228986-G-A
• chr8-53228986-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000522508.1(OPRK1):​n.*1277C>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 0.0135 in 220,468 control chromosomes in the GnomAD database, including 33 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 0.013 (26 hom., cov: 33)
  • Exomes 𝑓: 0.015 (7 hom.)
• Consequence: OPRK1 ENST00000522508.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• 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]

LOC105375836 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0129 (1971/152352) while in subpopulation AMR AF = 0.0208 (319/15306). AF 95% confidence interval is 0.019. There are 26 homozygotes in GnomAd4. There are 981 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	NM_000912.5	MANE Select	c.*311C>T		3_prime_UTR	Exon 4 of 4	NP_000903.2
	LOC105375836	NR_188096.1		n.1698G>A		non_coding_transcript_exon	Exon 3 of 3
	OPRK1	NM_001318497.2		c.*224C>T		3_prime_UTR	Exon 4 of 4	NP_001305426.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPRK1	ENST00000522508.1	TSL:1	n.*1277C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000428231.1
	OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.*311C>T		3_prime_UTR	Exon 4 of 4	ENSP00000265572.3
	OPRK1	ENST00000522508.1	TSL:1	n.*1277C>T		3_prime_UTR	Exon 5 of 5	ENSP00000428231.1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1972 AN: 152234 Hom.: 26 Cov.: 33

Gnomad AFR AF: 0.00313

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0182

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0148 AC: 1011 AN: 68116 Hom.: 7 Cov.: 0 AF XY: 0.0148 AC XY: 509 AN XY: 34444

African (AFR) AF: 0.00160 AC: 4 AN: 2494

American (AMR) AF: 0.0111 AC: 37 AN: 3348

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 45 AN: 2626

East Asian (EAS) AF: 0.00 AC: 0 AN: 4858

South Asian (SAS) AF: 0.00689 AC: 13 AN: 1888

European-Finnish (FIN) AF: 0.00947 AC: 33 AN: 3484

Middle Eastern (MID) AF: 0.0282 AC: 10 AN: 354

European-Non Finnish (NFE) AF: 0.0183 AC: 817 AN: 44572

Other (OTH) AF: 0.0116 AC: 52 AN: 4492

GnomAD4 genome AF: 0.0129 AC: 1971 AN: 152352 Hom.: 26 Cov.: 33 AF XY: 0.0132 AC XY: 981 AN XY: 74498

African (AFR) AF: 0.00313 AC: 130 AN: 41592

American (AMR) AF: 0.0208 AC: 319 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0108 AC: 52 AN: 4828

European-Finnish (FIN) AF: 0.00603 AC: 64 AN: 10612

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0182 AC: 1238 AN: 68044

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0137 Hom.: 6

Bravo AF: 0.0131

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		0.28
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: rs35373196; hg19: chr8-54141546;