rs1799971

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000914.5(OPRM1):c.118A>G(p.Asn40Asp) variant causes a missense change. The variant allele was found at a frequency of 0.151 in 1,613,692 control chromosomes in the GnomAD database, including 23,773 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,drug response (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1909 hom., cov: 32)

Exomes 𝑓: 0.15 ( 21864 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Uncertain significance; drug response no assertion criteria provided U:1O:1

Conservation

PhyloP100: 4.31

Publications

1317 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002016455).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.118A>G	p.Asn40Asp	missense_variant	Exon 1 of 4	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.118A>G	p.Asn40Asp	missense_variant	Exon 1 of 4	1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19734

AN:

152054

Hom.:

1912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.391

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.188

AC:

46959

AN:

249224

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.0244

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.372

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.153

AC:

223836

AN:

1461520

Hom.:

21864

Cov.:

AF XY:

0.159

AC XY:

115536

AN XY:

726998

show subpopulations

African (AFR)

AF:

0.0231

AC:

773

AN:

33470

American (AMR)

AF:

0.205

AC:

9181

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.190

AC:

4968

AN:

26134

East Asian (EAS)

AF:

0.413

AC:

16372

AN:

39680

South Asian (SAS)

AF:

0.357

AC:

30790

AN:

86246

European-Finnish (FIN)

AF:

0.197

AC:

10534

AN:

53390

Middle Eastern (MID)

AF:

0.154

AC:

886

AN:

5766

European-Non Finnish (NFE)

AF:

0.126

AC:

140462

AN:

1111738

Other (OTH)

AF:

0.163

AC:

9870

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

11053

22105

33158

44210

55263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5420

10840

16260

21680

27100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.130

AC:

19716

AN:

152172

Hom.:

1909

Cov.:

AF XY:

0.141

AC XY:

10499

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0292

AC:

1215

AN:

41568

American (AMR)

AF:

0.190

AC:

2904

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

609

AN:

3464

East Asian (EAS)

AF:

0.391

AC:

2008

AN:

5140

South Asian (SAS)

AF:

0.379

AC:

1829

AN:

4820

European-Finnish (FIN)

AF:

0.199

AC:

2106

AN:

10590

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8578

AN:

68006

Other (OTH)

AF:

0.138

AC:

291

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

805

1609

2414

3218

4023

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.133

Hom.:

8295

Bravo

AF:

0.120

TwinsUK

AF:

0.129

AC:

479

ALSPAC

AF:

0.127

AC:

489

ESP6500AA

AF:

0.0306

AC:

122

ESP6500EA

AF:

0.129

AC:

1070

ExAC

AF:

0.185

AC:

22379

Asia WGS

AF:

0.377

AC:

1311

AN:

3478

EpiCase

AF:

0.132

EpiControl

AF:

0.136

ClinVar

Significance: Uncertain significance; drug response

Submissions summary: Uncertain:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Opioid dependence, susceptibility to, 1

Uncertain:1

Jun 30, 2009

OMIM

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:literature only

- -

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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;.;T;T;.;.;.;.;.;.;.;.

Eigen

Benign

-0.011

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.69

T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

.;.;.;N;N;N;N;N;N;N;N;N

PhyloP100

4.3

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.1

N;N;.;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.024

D;D;.;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;T;D;D;D;T;D;D;D

Polyphen

0.081, 0.23, 0.0070, 0.73, 0.49, 0.95, 0.0010, 0.22, 0.0030

.;B;.;B;B;P;P;P;B;P;B;B

Vest4

0.18, 0.097, 0.17, 0.18, 0.19, 0.19, 0.20, 0.22, 0.19, 0.19

MPC

0.11

ClinPred

0.028

GERP RS

5.8

PromoterAI

0.097

Neutral

(source)

Varity_R

0.17

gMVP

0.43

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over