dbSNP rs7820807: OPRK1:c.*2996A>G (chr8-53226301-T-C) – 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.*2996A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,108 control chromosomes in the GnomAD database, including 3,420 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 0.18 ( 3420 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

OPRK1
NM_000912.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.751

Publications

7 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
OPRK1	NM_000912.5 link	c.*2996A>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000265572.8	NP_000903.2	P41145-1
OPRK1	NM_001318497.2 link	c.*2909A>G	3_prime_UTR_variant	Exon 4 of 4		NP_001305426.1	P41145A0A5F9ZI09
OPRK1	NM_001282904.2 link	c.*2996A>G	3_prime_UTR_variant	Exon 5 of 5		NP_001269833.1	P41145-2
LOC105375836	NR_188096.1 link	n.640-1627T>C	intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPRK1	ENST00000265572.8 link	c.*2996A>G	3_prime_UTR_variant	Exon 4 of 4	1	NM_000912.5	ENSP00000265572.3	P41145-1
OPRK1	ENST00000673285.2 link	c.*2909A>G	3_prime_UTR_variant	Exon 4 of 4			ENSP00000500765.2	A0A5F9ZI09
ENSG00000254687	ENST00000524425.1 link	n.670+9797T>C	intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

27358

AN:

151986

Hom.:

3408

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.231

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.0706

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.0890

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0958

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.180

AC:

27418

AN:

152104

Hom.:

3420

Cov.:

AF XY:

0.179

AC XY:

13307

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.348

AC:

14443

AN:

41452

American (AMR)

AF:

0.231

AC:

3532

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3472

East Asian (EAS)

AF:

0.0704

AC:

364

AN:

5172

South Asian (SAS)

AF:

0.105

AC:

508

AN:

4828

European-Finnish (FIN)

AF:

0.0890

AC:

944

AN:

10606

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0958

AC:

6513

AN:

67996

Other (OTH)

AF:

0.176

AC:

373

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1033

2065

3098

4130

5163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.147

Hom.:

785

Bravo

AF:

0.199

Asia WGS

AF:

0.113

AC:

393

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.53

(source)

DANN

Benign

0.76

PhyloP100

-0.75

Mutation Taster

=100/0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over