10-129710868-T-C

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

Publications

5 publications found
Variant links:
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]

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=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MGMTNM_002412.5 linkc.274+2825T>C intron_variant Intron 3 of 4 ENST00000651593.1 NP_002403.3
LOC105378560XR_946467.3 linkn.2819T>C non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MGMTENST00000651593.1 linkc.274+2825T>C intron_variant Intron 3 of 4 NM_002412.5 ENSP00000498729.1 P16455
MGMTENST00000306010.8 linkc.367+2825T>C intron_variant Intron 3 of 4 1 ENSP00000302111.7 B4DEE8
MGMTENST00000462672.1 linkn.435+2825T>C intron_variant Intron 2 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.346
AC:
52528
AN:
152008
Hom.:
9271
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.342
Gnomad AMI
AF:
0.208
Gnomad AMR
AF:
0.319
Gnomad ASJ
AF:
0.281
Gnomad EAS
AF:
0.540
Gnomad SAS
AF:
0.378
Gnomad FIN
AF:
0.338
Gnomad MID
AF:
0.351
Gnomad NFE
AF:
0.343
Gnomad OTH
AF:
0.332
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.345
AC:
52551
AN:
152126
Hom.:
9275
Cov.:
33
AF XY:
0.345
AC XY:
25660
AN XY:
74382
show subpopulations
African (AFR)
AF:
0.342
AC:
14181
AN:
41490
American (AMR)
AF:
0.319
AC:
4868
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.281
AC:
974
AN:
3470
East Asian (EAS)
AF:
0.540
AC:
2789
AN:
5162
South Asian (SAS)
AF:
0.377
AC:
1821
AN:
4828
European-Finnish (FIN)
AF:
0.338
AC:
3576
AN:
10588
Middle Eastern (MID)
AF:
0.357
AC:
105
AN:
294
European-Non Finnish (NFE)
AF:
0.343
AC:
23335
AN:
67984
Other (OTH)
AF:
0.337
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:
0.332
Hom.:
10328
Bravo
AF:
0.343
Asia WGS
AF:
0.485
AC:
1685
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.55
DANN
Benign
0.55
PhyloP100
-0.31
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: rs2053139; hg19: chr10-131509132; API