Genetic Variant OPRM1:c.*4A>G (chr6-154107567-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001145286.3(OPRM1):c.*4A>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 0.905 in 718,432 control chromosomes in the GnomAD database, including 294,828 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 0.87 ( 58128 hom., cov: 32)

Exomes 𝑓: 0.91 ( 236700 hom. )

Consequence

OPRM1
NM_001145286.3 3_prime_UTR

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.543

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:

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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=-1.03).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.1165-11116A>G		intron_variant	Intron 3 of 3	ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 link	c.1165-11116A>G		intron_variant	Intron 3 of 3	1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.872

AC:

132555

AN:

152084

Hom.:

58112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.873

Gnomad AMR

AF:

0.920

Gnomad ASJ

AF:

0.886

Gnomad EAS

AF:

0.983

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.877

Gnomad MID

AF:

0.927

Gnomad NFE

AF:

0.905

Gnomad OTH

AF:

0.892

GnomAD3 exomes

AF:

0.914

AC:

138482

AN:

151560

Hom.:

63439

AF XY:

0.919

AC XY:

74062

AN XY:

80616

show subpopulations

Gnomad AFR exome

AF:

0.768

Gnomad AMR exome

AF:

0.916

Gnomad ASJ exome

AF:

0.887

Gnomad EAS exome

AF:

0.980

Gnomad SAS exome

AF:

0.974

Gnomad FIN exome

AF:

0.880

Gnomad NFE exome

AF:

0.909

Gnomad OTH exome

AF:

0.920

GnomAD4 exome

AF:

0.913

AC:

517207

AN:

566230

Hom.:

236700

Cov.:

AF XY:

0.918

AC XY:

280344

AN XY:

305464

show subpopulations

Gnomad4 AFR exome

AF:

0.775

Gnomad4 AMR exome

AF:

0.915

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

0.978

Gnomad4 SAS exome

AF:

0.975

Gnomad4 FIN exome

AF:

0.885

Gnomad4 NFE exome

AF:

0.907

Gnomad4 OTH exome

AF:

0.910

GnomAD4 genome

AF:

0.871

AC:

132620

AN:

152202

Hom.:

58128

Cov.:

AF XY:

0.873

AC XY:

64938

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.769

Gnomad4 AMR

AF:

0.920

Gnomad4 ASJ

AF:

0.886

Gnomad4 EAS

AF:

0.983

Gnomad4 SAS

AF:

0.974

Gnomad4 FIN

AF:

0.877

Gnomad4 NFE

AF:

0.905

Gnomad4 OTH

AF:

0.893

Alfa

AF:

0.901

Hom.:

99659

Bravo

AF:

0.871

Asia WGS

AF:

0.964

AC:

3355

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- 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

-1.0

CADD

Benign

2.0

DANN

Benign

0.24

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