rs623956

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000414028.6(OPRM1):​c.*1096A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 984,140 control chromosomes in the GnomAD database, including 29,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.21 ( 3484 hom., cov: 32)
Exomes 𝑓: 0.25 ( 26036 hom. )

Consequence

OPRM1
ENST00000414028.6 3_prime_UTR

Scores

2

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.184

Publications

8 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRM1NM_000914.5 linkc.1165-9792A>G intron_variant Intron 3 of 3 ENST00000330432.12 NP_000905.3 P35372-1G8XRH5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OPRM1ENST00000330432.12 linkc.1165-9792A>G intron_variant Intron 3 of 3 1 NM_000914.5 ENSP00000328264.7 P35372-1

Frequencies

GnomAD3 genomes
AF:
0.207
AC:
31407
AN:
152048
Hom.:
3481
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.168
Gnomad AMI
AF:
0.269
Gnomad AMR
AF:
0.189
Gnomad ASJ
AF:
0.197
Gnomad EAS
AF:
0.0846
Gnomad SAS
AF:
0.145
Gnomad FIN
AF:
0.188
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.251
Gnomad OTH
AF:
0.190
GnomAD4 exome
AF:
0.248
AC:
206463
AN:
831974
Hom.:
26036
Cov.:
23
AF XY:
0.248
AC XY:
95381
AN XY:
384268
show subpopulations
African (AFR)
AF:
0.157
AC:
2467
AN:
15762
American (AMR)
AF:
0.169
AC:
166
AN:
984
Ashkenazi Jewish (ASJ)
AF:
0.197
AC:
1016
AN:
5146
East Asian (EAS)
AF:
0.0958
AC:
347
AN:
3622
South Asian (SAS)
AF:
0.150
AC:
2474
AN:
16444
European-Finnish (FIN)
AF:
0.225
AC:
62
AN:
276
Middle Eastern (MID)
AF:
0.244
AC:
395
AN:
1620
European-Non Finnish (NFE)
AF:
0.254
AC:
193253
AN:
760858
Other (OTH)
AF:
0.230
AC:
6283
AN:
27262
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.484
Heterozygous variant carriers
0
7530
15059
22589
30118
37648
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
8820
17640
26460
35280
44100
<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:
0.207
AC:
31440
AN:
152166
Hom.:
3484
Cov.:
32
AF XY:
0.201
AC XY:
14966
AN XY:
74402
show subpopulations
African (AFR)
AF:
0.168
AC:
6975
AN:
41504
American (AMR)
AF:
0.189
AC:
2893
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.197
AC:
683
AN:
3468
East Asian (EAS)
AF:
0.0847
AC:
439
AN:
5186
South Asian (SAS)
AF:
0.146
AC:
702
AN:
4818
European-Finnish (FIN)
AF:
0.188
AC:
1997
AN:
10600
Middle Eastern (MID)
AF:
0.228
AC:
67
AN:
294
European-Non Finnish (NFE)
AF:
0.251
AC:
17033
AN:
67978
Other (OTH)
AF:
0.192
AC:
406
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1264
2528
3792
5056
6320
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
332
664
996
1328
1660
<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:
0.230
Hom.:
555
Bravo
AF:
0.204
Asia WGS
AF:
0.122
AC:
426
AN:
3478

ClinVar

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

Submissions by phenotype

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
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.49
DANN
Benign
0.50
PhyloP100
-0.18
Mutation Taster
=100/0
polymorphism (auto)

Splicing

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

Publications

Other links and lift over

dbSNP: rs623956; hg19: chr6-154430026; API