rs17174794

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000914.5(OPRM1):c.440C>G(p.Ser147Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,613,352 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0064 ( 42 hom. )

Consequence

OPRM1
NM_000914.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 7.91

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015153289).

BP6

Variant 6-154089975-C-G is Benign according to our data. Variant chr6-154089975-C-G is described in ClinVar as [Benign]. Clinvar id is 252543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPRM1	NM_000914.5 link	c.440C>G	p.Ser147Cys	missense_variant	Exon 2 of 4	ENST00000330432.12	NP_000905.3	P35372-1G8XRH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPRM1	ENST00000330432.12 link	c.440C>G	p.Ser147Cys	missense_variant	Exon 2 of 4	1	NM_000914.5	ENSP00000328264.7		P35372-1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00685

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00414

AC:

1033

AN:

249580

Hom.:

AF XY:

0.00387

AC XY:

524

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00177

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00269

Gnomad NFE exome

AF:

0.00742

Gnomad OTH exome

AF:

0.00379

GnomAD4 exome

AF:

0.00640

AC:

9356

AN:

1461056

Hom.:

Cov.:

AF XY:

0.00613

AC XY:

4458

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.00778

Gnomad4 OTH exome

AF:

0.00596

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152296

Hom.:

Cov.:

AF XY:

0.00365

AC XY:

272

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00685

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00578

Hom.:

Bravo

AF:

0.00401

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00189

AC:

ESP6500EA

AF:

0.00658

AC:

ExAC

AF:

0.00460

AC:

558

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00578

EpiControl

AF:

0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 12, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

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

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.;D;D;D;D;D;D;D;D;D;D;D;.;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.015

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

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

.;.;.;.;M;M;M;M;M;M;M;M;M;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.4

D;D;D;.;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

D;D;D;.;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.012

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

Polyphen

1.0

D;.;.;.;D;D;D;D;D;D;D;D;D;.;.

Vest4

0.88

MVP

0.66

MPC

0.33

ClinPred

0.011

GERP RS

5.8

Varity_R

0.86

gMVP

0.80

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over