Variant rs6912029 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000360422.8(OPRM1):c.15G>T(p.Gln5His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.05 in 1,545,042 control chromosomes in the GnomAD database, including 2,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.061 ( 397 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2019 hom. )

Consequence

OPRM1
ENST00000360422.8 missense

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.376

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 (MetaRNN=0.001701355).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 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.-172G>T		5_prime_UTR_variant	1/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.-172G>T		5_prime_UTR_variant	1/4	1	NM_000914.5	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.0609

AC:

9260

AN:

152122

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.0943

Gnomad SAS

AF:

0.0574

Gnomad FIN

AF:

0.0298

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0439

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0441

AC:

6666

AN:

151002

Hom.:

219

AF XY:

0.0448

AC XY:

3575

AN XY:

79736

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00989

Gnomad EAS exome

AF:

0.0948

Gnomad SAS exome

AF:

0.0510

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0433

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0488

AC:

67934

AN:

1392802

Hom.:

2019

Cov.:

AF XY:

0.0488

AC XY:

33478

AN XY:

686016

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0166

Gnomad4 ASJ exome

AF:

0.00895

Gnomad4 EAS exome

AF:

0.0943

Gnomad4 SAS exome

AF:

0.0510

Gnomad4 FIN exome

AF:

0.0317

Gnomad4 NFE exome

AF:

0.0480

Gnomad4 OTH exome

AF:

0.0475

GnomAD4 genome

AF:

0.0609

AC:

9269

AN:

152240

Hom.:

397

Cov.:

AF XY:

0.0599

AC XY:

4462

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.112

Gnomad4 AMR

AF:

0.0253

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.0937

Gnomad4 SAS

AF:

0.0566

Gnomad4 FIN

AF:

0.0298

Gnomad4 NFE

AF:

0.0439

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0441

Hom.:

285

Bravo

AF:

0.0633

TwinsUK

AF:

0.0507

AC:

188

ALSPAC

AF:

0.0519

AC:

200

ESP6500AA

AF:

0.107

AC:

148

ESP6500EA

AF:

0.0409

AC:

130

ExAC

AF:

0.0230

AC:

1206

Asia WGS

AF:

0.0770

AC:

270

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_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.65

Cadd

Benign

7.9

Dann

Benign

0.64

DEOGEN2

Benign

0.0050

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0017

MutationTaster

Benign

1.0

P;P;P;P;P;P

Vest4

0.17

GERP RS

3.9

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