10-129710868-T-C
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002412.5(MGMT):c.274+2825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,126 control chromosomes in the GnomAD database, including 9,275 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 0.35 ( 9275 hom., cov: 33)
Consequence
MGMT
NM_002412.5 intron
NM_002412.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.314
Publications
5 publications found
Genes affected
MGMT (HGNC:7059): (O-6-methylguanine-DNA methyltransferase) Alkylating agents are potent carcinogens that can result in cell death, mutation and cancer. The protein encoded by this gene is a DNA repair protein that is involved in cellular defense against mutagenesis and toxicity from alkylating agents. The protein catalyzes transfer of methyl groups from O(6)-alkylguanine and other methylated moieties of the DNA to its own molecule, which repairs the toxic lesions. Methylation of the genes promoter has been associated with several cancer types, including colorectal cancer, lung cancer, lymphoma and glioblastoma. [provided by RefSeq, Sep 2015]
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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=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MGMT | ENST00000651593.1 | c.274+2825T>C | intron_variant | Intron 3 of 4 | NM_002412.5 | ENSP00000498729.1 | ||||
MGMT | ENST00000306010.8 | c.367+2825T>C | intron_variant | Intron 3 of 4 | 1 | ENSP00000302111.7 | ||||
MGMT | ENST00000462672.1 | n.435+2825T>C | intron_variant | Intron 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.346 AC: 52528AN: 152008Hom.: 9271 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
52528
AN:
152008
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.345 AC: 52551AN: 152126Hom.: 9275 Cov.: 33 AF XY: 0.345 AC XY: 25660AN XY: 74382 show subpopulations
GnomAD4 genome
AF:
AC:
52551
AN:
152126
Hom.:
Cov.:
33
AF XY:
AC XY:
25660
AN XY:
74382
show subpopulations
African (AFR)
AF:
AC:
14181
AN:
41490
American (AMR)
AF:
AC:
4868
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
AC:
974
AN:
3470
East Asian (EAS)
AF:
AC:
2789
AN:
5162
South Asian (SAS)
AF:
AC:
1821
AN:
4828
European-Finnish (FIN)
AF:
AC:
3576
AN:
10588
Middle Eastern (MID)
AF:
AC:
105
AN:
294
European-Non Finnish (NFE)
AF:
AC:
23335
AN:
67984
Other (OTH)
AF:
AC:
713
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1781
3563
5344
7126
8907
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
514
1028
1542
2056
2570
<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:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1685
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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