chr6-154047863-G-A

Variant summary

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

The NM_000914.5(OPRM1):​c.290+8029G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 152,234 control chromosomes in the GnomAD database, including 420 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.059 ( 420 hom., cov: 32)

Consequence

OPRM1
NM_000914.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.28

Publications

9 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=-0.95).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OPRM1NM_000914.5 linkc.290+8029G>A intron_variant Intron 1 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.290+8029G>A intron_variant Intron 1 of 3 1 NM_000914.5 ENSP00000328264.7 P35372-1

Frequencies

GnomAD3 genomes
AF:
0.0591
AC:
8991
AN:
152116
Hom.:
422
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0148
Gnomad AMI
AF:
0.0373
Gnomad AMR
AF:
0.0845
Gnomad ASJ
AF:
0.103
Gnomad EAS
AF:
0.175
Gnomad SAS
AF:
0.189
Gnomad FIN
AF:
0.0350
Gnomad MID
AF:
0.104
Gnomad NFE
AF:
0.0636
Gnomad OTH
AF:
0.0688
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0590
AC:
8984
AN:
152234
Hom.:
420
Cov.:
32
AF XY:
0.0611
AC XY:
4546
AN XY:
74434
show subpopulations
African (AFR)
AF:
0.0148
AC:
614
AN:
41552
American (AMR)
AF:
0.0844
AC:
1290
AN:
15292
Ashkenazi Jewish (ASJ)
AF:
0.103
AC:
358
AN:
3464
East Asian (EAS)
AF:
0.175
AC:
908
AN:
5178
South Asian (SAS)
AF:
0.188
AC:
906
AN:
4824
European-Finnish (FIN)
AF:
0.0350
AC:
371
AN:
10590
Middle Eastern (MID)
AF:
0.109
AC:
32
AN:
294
European-Non Finnish (NFE)
AF:
0.0636
AC:
4325
AN:
68012
Other (OTH)
AF:
0.0690
AC:
146
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
413
825
1238
1650
2063
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
114
228
342
456
570
<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:
0.0633
Hom.:
594
Bravo
AF:
0.0601
Asia WGS
AF:
0.149
AC:
517
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.30
DANN
Benign
0.52
PhyloP100
-1.3
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs4870266; hg19: chr6-154368998; COSMIC: COSV57674304; API