Variant rs11575856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000914.5(OPRM1):c.877G>A(p.Val293Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000397 in 1,614,048 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010830998).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.877G>A	p.Val293Ile	missense_variant	3/4	ENST00000330432.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPRM1	ENST00000330432.12 linkuse as main transcript	c.877G>A	p.Val293Ile	missense_variant	3/4	1	NM_000914.5	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.000579

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00847

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000996

AC:

249

AN:

250074

Hom.:

AF XY:

0.000945

AC XY:

128

AN XY:

135484

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00995

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.000836

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.000494

GnomAD4 exome

AF:

0.000379

AC:

554

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000388

AC XY:

282

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00650

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.000572

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00830

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000552

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000848

AC:

103

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.010

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.89

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.74

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

MetaRNN

Benign

0.011

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.42

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

MutationTaster

Benign

0.83

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.17

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

REVEL

Benign

0.069

Sift

Benign

0.48

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

Sift4G

Benign

0.56

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

Polyphen

0.23

B;.;.;.;B;B;B;B;B;B;B;B;B;.;.

Vest4

0.13

MVP

0.085

MPC

0.055

ClinPred

0.0069

GERP RS

3.1

Varity_R

0.051

gMVP

0.48

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over