Variant rs9282821 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000914.5(OPRM1):c.1164+1768A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,566,816 control chromosomes in the GnomAD database, including 272,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.55 ( 23725 hom., cov: 32)

Exomes 𝑓: 0.59 ( 248798 hom. )

Consequence

OPRM1
NM_000914.5 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.0730

Variant links:

Genes affected

OPRM1 (HGNC:8156): (opioid receptor mu 1) This gene encodes one of at least three opioid receptors in humans; the mu opioid receptor (MOR). The MOR is the principal target of endogenous opioid peptides and opioid analgesic agents such as beta-endorphin and enkephalins. The MOR also has an important role in dependence to other drugs of abuse, such as nicotine, cocaine, and alcohol via its modulation of the dopamine system. The NM_001008503.2:c.118A>G allele has been associated with opioid and alcohol addiction and variations in pain sensitivity but evidence for it having a causal role is conflicting. Multiple transcript variants encoding different isoforms have been found for this gene. Though the canonical MOR belongs to the superfamily of 7-transmembrane-spanning G-protein-coupled receptors some isoforms of this gene have only 6 transmembrane domains. [provided by RefSeq, Oct 2013]

OPRM1 links:

OPRM1 (HGNC:):

OPRM1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.1164+1768A>C		intron_variant		ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.1164+1768A>C		intron_variant		1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83821

AN:

151858

Hom.:

23735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.552

Gnomad ASJ

AF:

0.600

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.744

Gnomad FIN

AF:

0.611

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.581

GnomAD3 exomes

AF:

0.606

AC:

140979

AN:

232546

Hom.:

43639

AF XY:

0.615

AC XY:

77551

AN XY:

126072

show subpopulations

Gnomad AFR exome

AF:

0.447

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.606

Gnomad EAS exome

AF:

0.784

Gnomad SAS exome

AF:

0.736

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.580

Gnomad OTH exome

AF:

0.608

GnomAD4 exome

AF:

0.590

AC:

834160

AN:

1414840

Hom.:

248798

Cov.:

AF XY:

0.594

AC XY:

415587

AN XY:

699630

show subpopulations

Gnomad4 AFR exome

AF:

0.441

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.607

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.731

Gnomad4 FIN exome

AF:

0.611

Gnomad4 NFE exome

AF:

0.577

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.552

AC:

83822

AN:

151976

Hom.:

23725

Cov.:

AF XY:

0.558

AC XY:

41450

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.551

Gnomad4 ASJ

AF:

0.600

Gnomad4 EAS

AF:

0.792

Gnomad4 SAS

AF:

0.743

Gnomad4 FIN

AF:

0.611

Gnomad4 NFE

AF:

0.574

Gnomad4 OTH

AF:

0.581

Alfa

AF:

0.525

Hom.:

5219

Bravo

AF:

0.543

Asia WGS

AF:

0.734

AC:

2553

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Tramadol response

Other:1

drug response, no assertion criteria provided

research

Bruce Budowle Laboratory, University of North Texas Health Science Center

Apr 28, 2018

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.6

DANN

Benign

0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over