rs35373196

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000912.5(OPRK1):​c.*311C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 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 NM_000912.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRK1	NM_000912.5	c.*311C>T		3_prime_UTR_variant	4/4	ENST00000265572.8	NP_000903.2
LOC105375836	XR_928877.2	n.1698G>A		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001282904.2	c.*311C>T		3_prime_UTR_variant	5/5		NP_001269833.1
OPRK1	NM_001318497.2	c.*224C>T		3_prime_UTR_variant	4/4		NP_001305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8	c.*311C>T		3_prime_UTR_variant	4/4	1	NM_000912.5	ENSP00000265572	P1
OPRK1	ENST00000522508.1	c.*1277C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000428231
	ENST00000524425.1	n.670+12482G>A		intron_variant, non_coding_transcript_variant		3
OPRK1	ENST00000673285.2	c.*224C>T		3_prime_UTR_variant	4/4			ENSP00000500765

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

Gnomad4 AFR exome AF: 0.00160

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00689

Gnomad4 FIN exome AF: 0.00947

Gnomad4 NFE exome AF: 0.0183

Gnomad4 OTH exome AF: 0.0116

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

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0182

Gnomad4 OTH AF: 0.0198

Alfa AF: 0.00715 Hom.: 2

Bravo AF: 0.0131

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs35373196; hg19: chr8-54141546;