Variant rs9282817 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000330432.12(OPRM1):c.188G>A(p.Gly63Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,262 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G63V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

OPRM1
ENST00000330432.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23082551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPRM1	NM_000914.5 linkuse as main transcript	c.188G>A	p.Gly63Asp	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.188G>A	p.Gly63Asp	missense_variant	1/4	1	NM_000914.5	ENSP00000328264	P1	P35372-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1458074

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725514

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0035

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

Eigen

Benign

-0.13

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.88

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

M_CAP

Benign

0.0068

MetaRNN

Benign

0.23

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

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

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

MutationTaster

Benign

0.99

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

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

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

REVEL

Benign

0.14

Sift

Benign

0.054

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

Sift4G

Benign

0.16

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

Polyphen

0.0030, 0.0, 0.0020, 0.0010

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

Vest4

0.18, 0.18, 0.18, 0.18, 0.19, 0.20, 0.20, 0.21, 0.20, 0.21, 0.20

MutPred

0.32

.;.;.;Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);Loss of catalytic residue at S64 (P = 0.063);

MVP

0.33

MPC

0.061

ClinPred

0.58

GERP RS

5.8

Varity_R

0.11

gMVP

0.51

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