rs62638690

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000914.5(OPRM1):c.575G>T(p.Cys192Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00666 in 1,614,054 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 42 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 6.69

Publications

20 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012341559).

BP6

Variant 6-154090110-G-T is Benign according to our data. Variant chr6-154090110-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 828413.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 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	UniProt
OPRM1	NM_000914.5	MANE Select	c.575G>T	p.Cys192Phe	missense	Exon 2 of 4	NP_000905.3	P35372-1
OPRM1	NM_001145279.4		c.854G>T	p.Cys285Phe	missense	Exon 4 of 6	NP_001138751.1	P35372-10
OPRM1	NM_001285524.1		c.854G>T	p.Cys285Phe	missense	Exon 3 of 5	NP_001272453.1	P35372-10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPRM1	ENST00000330432.12	TSL:1 MANE Select	c.575G>T	p.Cys192Phe	missense	Exon 2 of 4	ENSP00000328264.7	P35372-1
OPRM1	ENST00000434900.6	TSL:1	c.854G>T	p.Cys285Phe	missense	Exon 4 of 6	ENSP00000394624.2	P35372-10
OPRM1	ENST00000360422.8	TSL:1	c.761G>T	p.Cys254Phe	missense	Exon 2 of 4	ENSP00000353598.5	L0E130

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00712

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00563

AC:

1400

AN:

248470

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.000775

Gnomad AMR exome

AF:

0.000898

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.0182

Gnomad NFE exome

AF:

0.00724

Gnomad OTH exome

AF:

0.00396

GnomAD4 exome

AF:

0.00679

AC:

9930

AN:

1461790

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

4777

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.000872

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

301

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000719

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0173

AC:

926

AN:

53404

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00734

AC:

8160

AN:

1111942

Other (OTH)

AF:

0.00679

AC:

410

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

507

1014

1520

2027

2534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.00542

AC:

826

AN:

152264

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41568

American (AMR)

AF:

0.00406

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0109

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0190

AC:

201

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00712

AC:

484

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

116

155

194

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:

0.00637

Hom.:

Bravo

AF:

0.00392

TwinsUK

AF:

0.00755

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00122

AC:

ESP6500EA

AF:

0.00792

AC:

ExAC

AF:

0.00531

AC:

643

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00634

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Tramadol response (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

PhyloP100

6.7

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.33

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.021

Polyphen

0.50

Vest4

0.56

MVP

0.86

MPC

0.19

ClinPred

0.032

GERP RS

5.8

Varity_R

0.84

gMVP

0.96

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over