Variant 6-154093428-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000229768.9(OPRM1):c.1323A>G(p.Gly441=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,612,778 control chromosomes in the GnomAD database, including 377,522 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 0.70 ( 37138 hom., cov: 31)

Exomes 𝑓: 0.68 ( 340384 hom. )

Consequence

OPRM1
ENST00000229768.9 synonymous

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.315

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP7

Synonymous conserved (PhyloP=-0.315 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 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+1956A>G		intron_variant		ENST00000330432.12	NP_000905.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.1164+1956A>G		intron_variant		1	NM_000914.5	ENSP00000328264	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.698

AC:

105623

AN:

151380

Hom.:

37125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.723

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.687

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.834

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.729

GnomAD3 exomes

AF:

0.720

AC:

179571

AN:

249392

Hom.:

65507

AF XY:

0.721

AC XY:

97565

AN XY:

135308

show subpopulations

Gnomad AFR exome

AF:

0.726

Gnomad AMR exome

AF:

0.778

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.826

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.658

Gnomad OTH exome

AF:

0.711

GnomAD4 exome

AF:

0.680

AC:

993073

AN:

1461280

Hom.:

340384

Cov.:

AF XY:

0.683

AC XY:

496529

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.775

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.891

Gnomad4 SAS exome

AF:

0.822

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.655

Gnomad4 OTH exome

AF:

0.694

GnomAD4 genome

AF:

0.698

AC:

105683

AN:

151498

Hom.:

37138

Cov.:

AF XY:

0.703

AC XY:

52030

AN XY:

73998

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.741

Gnomad4 ASJ

AF:

0.687

Gnomad4 EAS

AF:

0.898

Gnomad4 SAS

AF:

0.833

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.652

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.674

Hom.:

73659

Bravo

AF:

0.707

Asia WGS

AF:

0.855

AC:

2974

AN:

3478

EpiCase

AF:

0.662

EpiControl

AF:

0.668

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

-0.82

CADD

Benign

0.31

DANN

Benign

0.43

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