Genetic Variant OPRK1:c.-298G>A (chr8-53251335-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000520287.5(OPRK1):c.-298G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 460,126 control chromosomes in the GnomAD database, including 472 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 0.044 ( 168 hom., cov: 32)

Exomes 𝑓: 0.040 ( 304 hom. )

Consequence

OPRK1
ENST00000520287.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.42

Publications

1 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:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
OPRK1	NM_000912.5 link	c.-49+113G>A	intron_variant	Intron 1 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2 link	c.-49+113G>A	intron_variant	Intron 1 of 3		NP_001305426.1
OPRK1	NM_001282904.2 link	c.-490+113G>A	intron_variant	Intron 1 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
OPRK1	ENST00000520287.5 link	c.-298G>A	5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000429706.1
OPRK1	ENST00000265572.8 link	c.-49+113G>A	intron_variant	Intron 1 of 3	1	NM_000912.5	ENSP00000265572.3
OPRK1	ENST00000522508.1 link	n.-49+113G>A	intron_variant	Intron 1 of 4	1		ENSP00000428231.1
OPRK1	ENST00000673285.2 link	c.-49+113G>A	intron_variant	Intron 1 of 3			ENSP00000500765.2

Frequencies

GnomAD3 genomes

AF:

0.0437

AC:

6647

AN:

152112

Hom.:

168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0628

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0333

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0455

Gnomad OTH

AF:

0.0382

GnomAD4 exome

AF:

0.0397

AC:

12221

AN:

307896

Hom.:

304

Cov.:

AF XY:

0.0395

AC XY:

6346

AN XY:

160486

show subpopulations

African (AFR)

AF:

0.0578

AC:

378

AN:

6536

American (AMR)

AF:

0.0193

AC:

153

AN:

7910

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

184

AN:

9830

East Asian (EAS)

AF:

0.0000518

AC:

AN:

19298

South Asian (SAS)

AF:

0.0398

AC:

1051

AN:

26430

European-Finnish (FIN)

AF:

0.0241

AC:

552

AN:

22902

Middle Eastern (MID)

AF:

0.0393

AC:

AN:

1502

European-Non Finnish (NFE)

AF:

0.0466

AC:

9066

AN:

194538

Other (OTH)

AF:

0.0410

AC:

777

AN:

18950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

541

1082

1624

2165

2706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.0437

AC:

6648

AN:

152230

Hom.:

168

Cov.:

AF XY:

0.0417

AC XY:

3101

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0627

AC:

2606

AN:

41536

American (AMR)

AF:

0.0261

AC:

399

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0225

AC:

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5158

South Asian (SAS)

AF:

0.0329

AC:

159

AN:

4828

European-Finnish (FIN)

AF:

0.0186

AC:

197

AN:

10608

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0455

AC:

3093

AN:

68002

Other (OTH)

AF:

0.0374

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

323

645

968

1290

1613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0197

Hom.:

Bravo

AF:

0.0447

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.78

(source)

DANN

Benign

0.80

PhyloP100

-1.4

PromoterAI

-0.022

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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