Variant rs1042753 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.151G>A(p.Asp51Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99

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=0.054998428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.151G>A	p.Asp51Asn	missense_variant	1/4	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.151G>A	p.Asp51Asn	missense_variant	1/4	1	NM_000914.5	ENSP00000328264	P1	P35372-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248948

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0089

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

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.0027

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0019

MetaRNN

Benign

0.055

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

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

MutationTaster

Benign

1.0

D;D;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.21

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

REVEL

Benign

0.072

Sift

Benign

0.17

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

Sift4G

Benign

0.53

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

Polyphen

0.0040, 0.0, 0.0010

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

Vest4

0.10, 0.15, 0.15, 0.17, 0.18, 0.18, 0.18, 0.12, 0.18

MutPred

0.27

.;.;.;Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);Gain of catalytic residue at D51 (P = 0.0152);

MVP

0.23

MPC

0.049

ClinPred

0.23

GERP RS

4.9

Varity_R

0.077

gMVP

0.32

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