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GeneBe

rs1799971

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM1BP4_StrongBA1

The NM_000914(OPRM1):c.118A>G(p.Asn40Asp) variant causes a missense change. The variant allele was found at a frequency of 0.13 in 152054 control chromosomes in the gnomAD Genomes database, including 1912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance,drug response (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1912 hom., cov: 32)
Exomes 𝑓: 0.19 ( 5913 hom. )

Consequence

OPRM1
NM_000914 missense

Scores

4
12

Clinical Significance

Uncertain significance; drug response no assertion criteria provided U:1O:1

Conservation

PhyloP100: 4.31

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

PM1
?
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity OPRM_HUMAN
BP4
?
Computational evidence support a benign effect (MetaRNN=0.002016455).
BA1
?
GnomAd highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPRM1NM_000914.5 linkuse as main transcriptc.118A>G p.Asn40Asp missense_variant 1/4 ENST00000330432.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OPRM1ENST00000330432.12 linkuse as main transcriptc.118A>G p.Asn40Asp missense_variant 1/41 NM_000914.5 P1P35372-1

Frequencies

GnomAD3 genomes
AF:
0.130
AC:
19734
AN:
152054
Hom.:
1912
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0293
Gnomad AMI
AF:
0.147
Gnomad AMR
AF:
0.190
Gnomad ASJ
AF:
0.176
Gnomad EAS
AF:
0.391
Gnomad SAS
AF:
0.380
Gnomad FIN
AF:
0.199
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.126
Gnomad OTH
AF:
0.139
GnomAD3 exomes
AF:
0.188
AC:
46959
AN:
249224
Hom.:
5913
AF XY:
0.196
AC XY:
26451
AN XY:
135238
show subpopulations
Gnomad AFR exome
AF:
0.0244
Gnomad AMR exome
AF:
0.215
Gnomad ASJ exome
AF:
0.187
Gnomad EAS exome
AF:
0.372
Gnomad SAS exome
AF:
0.363
Gnomad FIN exome
AF:
0.198
Gnomad NFE exome
AF:
0.125
Gnomad OTH exome
AF:
0.180
GnomAD4 exome
AF:
0.153
AC:
223836
AN:
1461520
Hom.:
21864
AF XY:
0.159
AC XY:
115536
AN XY:
726998
show subpopulations
Gnomad4 AFR exome
AF:
0.0231
Gnomad4 AMR exome
AF:
0.205
Gnomad4 ASJ exome
AF:
0.190
Gnomad4 EAS exome
AF:
0.413
Gnomad4 SAS exome
AF:
0.357
Gnomad4 FIN exome
AF:
0.197
Gnomad4 NFE exome
AF:
0.126
Gnomad4 OTH exome
AF:
0.163
Alfa
AF:
0.139
Hom.:
4404
Bravo
AF:
0.120
TwinsUK
AF:
0.129
AC:
479
ALSPAC
AF:
0.127
AC:
489
ESP6500AA
AF:
0.0306
AC:
122
ESP6500EA
AF:
0.129
AC:
1070
ExAC
AF:
0.185
AC:
22379
Asia WGS
AF:
0.377
AC:
1311
AN:
3478
EpiCase
AF:
0.132
EpiControl
AF:
0.136

ClinVar

Significance: Uncertain significance; drug response
Submissions summary: Uncertain:1Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Opioid dependence, susceptibility to, 1 Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyOMIMJun 30, 2009- -
Tramadol response Other:1
drug response, no assertion criteria providedresearchBruce Budowle Laboratory, University of North Texas Health Science CenterApr 28, 2018- 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
Benign
0.15
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.44
Cadd
Uncertain
24
Dann
Uncertain
1.0
Eigen
Benign
-0.011
Eigen_PC
Benign
0.18
FATHMM_MKL
Benign
0.027
N
LIST_S2
Benign
0.69
T;T;T;T;T;T;T;T;T;T;T;T
MetaRNN
Benign
0.0020
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
0.0030
P;P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-2.1
N;N;.;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.10
Sift
Uncertain
0.024
D;D;.;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.010
D;D;D;D;T;D;D;D;T;D;D;D
Polyphen
0.081, 0.23, 0.0070, 0.73, 0.49, 0.95, 0.0010, 0.22, 0.0030
.;B;.;B;B;P;P;P;B;P;B;B
Vest4
0.18, 0.097, 0.17, 0.18, 0.19, 0.19, 0.20, 0.22, 0.19, 0.19
MPC
0.11
ClinPred
0.028
T
GERP RS
5.8
Varity_R
0.17
gMVP
0.43

Splicing

Find out SpliceAI and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1799971; hg19: chr6-154360797; COSMIC: COSV57673061;