Genetic Variant OPRK1:n.*1277C>T (chr8-53228986-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000522508.1(OPRK1):n.*1277C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 220,468 control chromosomes in the GnomAD database, including 33 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 0.013 ( 26 hom., cov: 33)

Exomes 𝑓: 0.015 ( 7 hom. )

Consequence

OPRK1
ENST00000522508.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Publications

3 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:

Genome browser will be placed here

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=-0.79).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0129 (1971/152352) while in subpopulation AMR AF = 0.0208 (319/15306). AF 95% confidence interval is 0.019. There are 26 homozygotes in GnomAd4. There are 981 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OPRK1	NM_000912.5	MANE Select	c.*311C>T	3_prime_UTR	Exon 4 of 4	NP_000903.2
LOC105375836	NR_188096.1		n.1698G>A	non_coding_transcript_exon	Exon 3 of 3
OPRK1	NM_001318497.2		c.*224C>T	3_prime_UTR	Exon 4 of 4	NP_001305426.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
OPRK1	ENST00000522508.1	TSL:1	n.*1277C>T	non_coding_transcript_exon	Exon 5 of 5	ENSP00000428231.1
OPRK1	ENST00000265572.8	TSL:1 MANE Select	c.*311C>T	3_prime_UTR	Exon 4 of 4	ENSP00000265572.3
OPRK1	ENST00000522508.1	TSL:1	n.*1277C>T	3_prime_UTR	Exon 5 of 5	ENSP00000428231.1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1972

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00313

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00603

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0148

AC:

1011

AN:

68116

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

509

AN XY:

34444

show subpopulations

African (AFR)

AF:

0.00160

AC:

AN:

2494

American (AMR)

AF:

0.0111

AC:

AN:

3348

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

AN:

2626

East Asian (EAS)

AF:

0.00

AC:

AN:

4858

South Asian (SAS)

AF:

0.00689

AC:

AN:

1888

European-Finnish (FIN)

AF:

0.00947

AC:

AN:

3484

Middle Eastern (MID)

AF:

0.0282

AC:

AN:

354

European-Non Finnish (NFE)

AF:

0.0183

AC:

817

AN:

44572

Other (OTH)

AF:

0.0116

AC:

AN:

4492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0129

AC:

1971

AN:

152352

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

981

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00313

AC:

130

AN:

41592

American (AMR)

AF:

0.0208

AC:

319

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0108

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00603

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0182

AC:

1238

AN:

68044

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.0137

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

(source)

DANN

Benign

0.66

PhyloP100

0.28

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over