rs17174801

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2

The NM_000914.5(OPRM1):c.454A>G(p.Asn152Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,614,090 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Publications

12 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:

ENSG00000299884 (HGNC:):

ENSG00000299884 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PrimateAI, PROVEAN [when BayesDel_addAF, BayesDel_noAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.019883275).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	NM_000914.5	MANE Select	c.454A>G	p.Asn152Asp	missense	Exon 2 of 4	NP_000905.3
OPRM1	NM_001145279.4		c.733A>G	p.Asn245Asp	missense	Exon 4 of 6	NP_001138751.1
OPRM1	NM_001285524.1		c.733A>G	p.Asn245Asp	missense	Exon 3 of 5	NP_001272453.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.454A>G	p.Asn152Asp	missense	Exon 2 of 4	ENSP00000328264.7
OPRM1	ENST00000434900.6	TSL:1	c.733A>G	p.Asn245Asp	missense	Exon 4 of 6	ENSP00000394624.2
OPRM1	ENST00000360422.8	TSL:1	c.640A>G	p.Asn214Asp	missense	Exon 2 of 4	ENSP00000353598.5

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

394

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00924

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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

GnomAD2 exomes

AF:

0.000693

AC:

173

AN:

249630

AF XY:

0.000576

show subpopulations

Gnomad AFR exome

AF:

0.0100

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1461754

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

207

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0119

AC:

398

AN:

33474

American (AMR)

AF:

0.000380

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111892

Other (OTH)

AF:

0.000546

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

101

126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00259

AC:

394

AN:

152336

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00921

AC:

383

AN:

41572

American (AMR)

AF:

0.000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00130

Hom.:

Bravo

AF:

0.00305

ESP6500AA

AF:

0.00797

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000767

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.033

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.36

MutationAssessor

Pathogenic

3.7

PhyloP100

9.3

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.46

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.96

MVP

0.75

MPC

0.35

ClinPred

0.11

GERP RS

5.8

Varity_R

0.97

gMVP

0.95

Mutation Taster

=7/93

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over