8-53229675-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000912.5(OPRK1):c.765C>T(p.Ser255=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,614,118 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00048 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (3 hom.)
• Consequence: OPRK1 NM_000912.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0230

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 8-53229675-G-A is Benign according to our data. Variant chr8-53229675-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.023 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRK1	NM_000912.5	c.765C>T	p.Ser255=	synonymous_variant	4/4	ENST00000265572.8
LOC105375836	XR_928877.2	n.2387G>A		non_coding_transcript_exon_variant	3/3
OPRK1	NM_001318497.2	c.765C>T	p.Ser255=	synonymous_variant	4/4
OPRK1	NM_001282904.2	c.498C>T	p.Ser166=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRK1	ENST00000265572.8	c.765C>T	p.Ser255=	synonymous_variant	4/4	1	NM_000912.5	P1
	ENST00000524425.1	n.671-12853G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000467 AC: 71 AN: 152130 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000641 AC: 161 AN: 251272 Hom.: 1 AF XY: 0.000736 AC XY: 100 AN XY: 135792

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000392

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000669

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.000510 AC: 745 AN: 1461870 Hom.: 3 Cov.: 31 AF XY: 0.000539 AC XY: 392 AN XY: 727234

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.00143

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000475

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000399

Gnomad4 OTH exome AF: 0.00109

GnomAD4 genome AF: 0.000479 AC: 73 AN: 152248 Hom.: 1 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74432

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000949 Hom.: 0

Bravo AF: 0.000608

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	2.7
Dann	Benign	0.79

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: rs139043596; hg19: chr8-54142235; COSMIC: COSV55570600;