Variant rs9322446 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000522236.1(OPRM1):c.-248G>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 0.149 in 984,764 control chromosomes in the GnomAD database, including 11,629 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 0.12 ( 1359 hom., cov: 32)

Exomes 𝑓: 0.15 ( 10270 hom. )

Consequence

OPRM1
ENST00000522236.1 5_prime_UTR

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.357

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.291-2259G>A		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.291-2259G>A		intron_variant		1	NM_000914.5	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18272

AN:

152054

Hom.:

1360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0600

Gnomad AMI

AF:

0.0768

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.0433

Gnomad SAS

AF:

0.0586

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.155

AC:

128781

AN:

832592

Hom.:

10270

Cov.:

AF XY:

0.154

AC XY:

59398

AN XY:

384510

show subpopulations

Gnomad4 AFR exome

AF:

0.0509

Gnomad4 AMR exome

AF:

0.0752

Gnomad4 ASJ exome

AF:

0.0831

Gnomad4 EAS exome

AF:

0.0369

Gnomad4 SAS exome

AF:

0.0651

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.120

AC:

18267

AN:

152172

Hom.:

1359

Cov.:

AF XY:

0.121

AC XY:

9008

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0598

Gnomad4 AMR

AF:

0.0925

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.0432

Gnomad4 SAS

AF:

0.0587

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.132

Hom.:

349

Bravo

AF:

0.109

Asia WGS

AF:

0.0410

AC:

143

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

-0.96

CADD

Benign

0.46

DANN

Benign

0.66

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

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