Variant 6-154093438-C-T 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.1333C>T(p.Leu445=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,612,816 control chromosomes in the GnomAD database, including 371,452 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 0.67 ( 34184 hom., cov: 31)

Exomes 𝑓: 0.68 ( 337268 hom. )

Consequence

OPRM1
ENST00000229768.9 synonymous

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.386

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=-0.79).

BP7

Synonymous conserved (PhyloP=0.386 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	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.1164+1966C>T		intron_variant		ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.1164+1966C>T		intron_variant		1	NM_000914.5	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.669

AC:

101319

AN:

151418

Hom.:

34180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.624

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.688

Gnomad EAS

AF:

0.898

Gnomad SAS

AF:

0.833

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.706

GnomAD3 exomes

AF:

0.713

AC:

177718

AN:

249284

Hom.:

64248

AF XY:

0.716

AC XY:

96791

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.773

Gnomad ASJ exome

AF:

0.684

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.824

Gnomad FIN exome

AF:

0.684

Gnomad NFE exome

AF:

0.657

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.676

AC:

988529

AN:

1461280

Hom.:

337268

Cov.:

AF XY:

0.680

AC XY:

494529

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.629

Gnomad4 AMR exome

AF:

0.770

Gnomad4 ASJ exome

AF:

0.686

Gnomad4 EAS exome

AF:

0.891

Gnomad4 SAS exome

AF:

0.820

Gnomad4 FIN exome

AF:

0.683

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.669

AC:

101357

AN:

151536

Hom.:

34184

Cov.:

AF XY:

0.676

AC XY:

50008

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.623

Gnomad4 AMR

AF:

0.730

Gnomad4 ASJ

AF:

0.688

Gnomad4 EAS

AF:

0.897

Gnomad4 SAS

AF:

0.832

Gnomad4 FIN

AF:

0.678

Gnomad4 NFE

AF:

0.652

Gnomad4 OTH

AF:

0.705

Alfa

AF:

0.665

Hom.:

67091

Bravo

AF:

0.675

Asia WGS

AF:

0.844

AC:

2934

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

-0.79

CADD

Benign

DANN

Benign

0.62

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