Genetic Variant OPRK1:c.610+77G>A (chr8-53234682-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 NM_000912.5(OPRK1):c.610+77G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 1,257,100 control chromosomes in the GnomAD database, including 1,443 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 ( 166 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1277 hom. )

Consequence

OPRK1
NM_000912.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

4 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:

ENSG00000254687 (HGNC:):

ENSG00000254687 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
OPRK1	NM_000912.5 link	c.610+77G>A	intron_variant	Intron 3 of 3	ENST00000265572.8	NP_000903.2
OPRK1	NM_001318497.2 link	c.610+77G>A	intron_variant	Intron 3 of 3		NP_001305426.1
OPRK1	NM_001282904.2 link	c.343+77G>A	intron_variant	Intron 4 of 4		NP_001269833.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRK1	ENST00000265572.8 link	c.610+77G>A		intron_variant	Intron 3 of 3	1	NM_000912.5	ENSP00000265572.3

Frequencies

GnomAD3 genomes

AF:

0.0441

AC:

6706

AN:

152138

Hom.:

166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0640

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0330

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0457

Gnomad OTH

AF:

0.0387

GnomAD4 exome

AF:

0.0447

AC:

49379

AN:

1104844

Hom.:

1277

AF XY:

0.0446

AC XY:

24697

AN XY:

554352

show subpopulations

African (AFR)

AF:

0.0619

AC:

1590

AN:

25706

American (AMR)

AF:

0.0194

AC:

715

AN:

36768

Ashkenazi Jewish (ASJ)

AF:

0.0181

AC:

360

AN:

19852

East Asian (EAS)

AF:

0.000186

AC:

AN:

37634

South Asian (SAS)

AF:

0.0374

AC:

2565

AN:

68572

European-Finnish (FIN)

AF:

0.0228

AC:

1073

AN:

47132

Middle Eastern (MID)

AF:

0.0364

AC:

177

AN:

4866

European-Non Finnish (NFE)

AF:

0.0500

AC:

40801

AN:

816538

Other (OTH)

AF:

0.0438

AC:

2091

AN:

47776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2372

4744

7116

9488

11860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1386

2772

4158

5544

6930

<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:

0.0440

AC:

6703

AN:

152256

Hom.:

166

Cov.:

AF XY:

0.0419

AC XY:

3117

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0639

AC:

2653

AN:

41542

American (AMR)

AF:

0.0262

AC:

401

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0326

AC:

157

AN:

4820

European-Finnish (FIN)

AF:

0.0186

AC:

198

AN:

10618

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0457

AC:

3106

AN:

68008

Other (OTH)

AF:

0.0378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

329

659

988

1318

1647

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:

0.0448

Hom.:

212

Bravo

AF:

0.0451

Asia WGS

AF:

0.0210

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

(source)

DANN

Benign

0.61

PhyloP100

0.084

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