Genetic Variant OPRM1:p.Ser85Ser (chr6-154039520-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000434900.6(OPRM1):c.255C>T(p.Ser85Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,594,948 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 12 hom. )

Consequence

OPRM1
ENST00000434900.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.47

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-154039520-C-T is Benign according to our data. Variant chr6-154039520-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 829269.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.47 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000434900.6. 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.-25C>T		5_prime_UTR	Exon 1 of 4	NP_000905.3
OPRM1	NM_001145279.4		c.255C>T	p.Ser85Ser	synonymous	Exon 3 of 6	NP_001138751.1
OPRM1	NM_001285524.1		c.255C>T	p.Ser85Ser	synonymous	Exon 2 of 5	NP_001272453.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OPRM1	ENST00000434900.6	TSL:1	c.255C>T	p.Ser85Ser	synonymous	Exon 3 of 6	ENSP00000394624.2
OPRM1	ENST00000360422.8	TSL:1	c.162C>T	p.Ser54Ser	synonymous	Exon 1 of 4	ENSP00000353598.5
OPRM1	ENST00000520282.5	TSL:1	c.120C>T	p.Ser40Ser	synonymous	Exon 2 of 3	ENSP00000430247.1

Frequencies

GnomAD3 genomes

AF:

0.00285

AC:

434

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00438

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.00525

GnomAD2 exomes

AF:

0.00351

AC:

757

AN:

215878

AF XY:

0.00350

show subpopulations

Gnomad AFR exome

AF:

0.000648

Gnomad AMR exome

AF:

0.00229

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00378

Gnomad NFE exome

AF:

0.00391

Gnomad OTH exome

AF:

0.00447

GnomAD4 exome

AF:

0.00376

AC:

5425

AN:

1442606

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

2629

AN XY:

715728

show subpopulations

African (AFR)

AF:

0.000754

AC:

AN:

33170

American (AMR)

AF:

0.00274

AC:

114

AN:

41576

Ashkenazi Jewish (ASJ)

AF:

0.0143

AC:

365

AN:

25558

East Asian (EAS)

AF:

0.0000516

AC:

AN:

38794

South Asian (SAS)

AF:

0.00261

AC:

217

AN:

83280

European-Finnish (FIN)

AF:

0.00338

AC:

175

AN:

51838

Middle Eastern (MID)

AF:

0.00956

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00381

AC:

4205

AN:

1103004

Other (OTH)

AF:

0.00448

AC:

267

AN:

59632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

376

752

1128

1504

1880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

166

332

498

664

830

<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:

0.00284

AC:

433

AN:

152342

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41592

American (AMR)

AF:

0.00438

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00433

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00312

AC:

212

AN:

68028

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00322

Hom.:

Bravo

AF:

0.00300

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

OPRM1: BP4, BP7

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance:drug response

Review Status:no assertion criteria provided

Collection Method:research

T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.20

(source)

DANN

Benign

0.87

PhyloP100

-1.5

PromoterAI

0.0010

Neutral

(source)

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over