dbSNP rs16918875: OPRK1:p.Val282Val (chr8-53229594-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000912.5(OPRK1):c.846C>T(p.Val282Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 1,614,034 control chromosomes in the GnomAD database, including 2,711 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 0.069 ( 546 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2165 hom. )

Consequence

OPRK1
NM_000912.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0250

Publications

17 publications found

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:

LOC105375836 (HGNC:):

LOC105375836 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=0.025 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5 link	c.846C>T	p.Val282Val	synonymous_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2	P41145-1
OPRK1	NM_001318497.2 link	c.846C>T	p.Val282Val	synonymous_variant	Exon 4 of 4		NP_001305426.1	P41145A0A5F9ZI09
OPRK1	NM_001282904.2 link	c.579C>T	p.Val193Val	synonymous_variant	Exon 5 of 5		NP_001269833.1	P41145-2
LOC105375836	NR_188096.1 link	n.2306G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8 link	c.846C>T	p.Val282Val	synonymous_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3		P41145-1

Frequencies

GnomAD3 genomes

AF:

0.0692

AC:

10523

AN:

152088

Hom.:

545

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0379

Gnomad ASJ

AF:

0.0202

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0334

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0579

GnomAD2 exomes

AF:

0.0429

AC:

10772

AN:

251210

AF XY:

0.0419

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.0243

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.0208

Gnomad NFE exome

AF:

0.0477

Gnomad OTH exome

AF:

0.0434

GnomAD4 exome

AF:

0.0490

AC:

71681

AN:

1461828

Hom.:

2165

Cov.:

AF XY:

0.0485

AC XY:

35297

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.153

AC:

5124

AN:

33478

American (AMR)

AF:

0.0251

AC:

1124

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

491

AN:

26134

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0372

AC:

3211

AN:

86254

European-Finnish (FIN)

AF:

0.0231

AC:

1233

AN:

53410

Middle Eastern (MID)

AF:

0.0425

AC:

245

AN:

5768

European-Non Finnish (NFE)

AF:

0.0514

AC:

57175

AN:

1111966

Other (OTH)

AF:

0.0508

AC:

3068

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

3917

7834

11752

15669

19586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2178

4356

6534

8712

10890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0692

AC:

10534

AN:

152206

Hom.:

546

Cov.:

AF XY:

0.0672

AC XY:

5004

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.149

AC:

6201

AN:

41484

American (AMR)

AF:

0.0379

AC:

580

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0202

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.0328

AC:

158

AN:

4818

European-Finnish (FIN)

AF:

0.0189

AC:

201

AN:

10620

Middle Eastern (MID)

AF:

0.0514

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0465

AC:

3162

AN:

68008

Other (OTH)

AF:

0.0568

AC:

120

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

483

966

1449

1932

2415

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0536

Hom.:

459

Bravo

AF:

0.0738

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0466

EpiControl

AF:

0.0495

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.5

(source)

DANN

Benign

0.79

PhyloP100

0.025

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over