chr8-53234771-T-C

Position:

chr8-53234771-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000912.5(OPRK1):c.598A>G(p.Lys200Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,609,364 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

Variant links:

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]

OPRK1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008436441).

BP6

Variant 8-53234771-T-C is Benign according to our data. Variant chr8-53234771-T-C is described in ClinVar as [Benign]. Clinvar id is 724740.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
OPRK1	NM_000912.5 linkuse as main transcript	c.598A>G	p.Lys200Glu	missense_variant	3/4	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2 linkuse as main transcript	c.598A>G	p.Lys200Glu	missense_variant	3/4		NP_001305426.1
OPRK1	NM_001282904.2 linkuse as main transcript	c.331A>G	p.Lys111Glu	missense_variant	4/5		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8 linkuse as main transcript	c.598A>G	p.Lys200Glu	missense_variant	3/4	1	NM_000912.5	ENSP00000265572	P1	P41145-1
	ENST00000524425.1 linkuse as main transcript	n.671-7757T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00569

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00143

GnomAD3 exomes

AF:

0.000423

AC:

106

AN:

250784

Hom.:

AF XY:

0.000354

AC XY:

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00628

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1457042

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

101

AN XY:

723682

show subpopulations

Gnomad4 AFR exome

AF:

0.00590

Gnomad4 AMR exome

AF:

0.000202

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.000249

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152322

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00568

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000292

Hom.:

Bravo

AF:

0.00189

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000445

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.072

.;.;T;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

T;T;.;.;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.0084

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.35

.;.;N;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.84

.;.;N;N;N

REVEL

Benign

0.083

Sift

Benign

0.24

.;.;T;T;T

Sift4G

Benign

0.92

T;T;T;T;T

Polyphen

0.078

.;.;B;.;B

Vest4

0.48

MVP

0.57

MPC

0.50

ClinPred

0.029

GERP RS

5.7

Varity_R

0.55

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over