chr10-129622012-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002412.5(MGMT):​c.125+85635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,070 control chromosomes in the GnomAD database, including 20,040 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 0.51 ( 20040 hom., cov: 33)

Consequence

MGMT
NM_002412.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.879
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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MGMTNM_002412.5 linkuse as main transcriptc.125+85635C>T intron_variant ENST00000651593.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MGMTENST00000651593.1 linkuse as main transcriptc.125+85635C>T intron_variant NM_002412.5 P1
MGMTENST00000306010.8 linkuse as main transcriptc.218+85635C>T intron_variant 1
ENST00000662900.1 linkuse as main transcriptn.2954G>A non_coding_transcript_exon_variant 4/4

Frequencies

GnomAD3 genomes
AF:
0.509
AC:
77298
AN:
151952
Hom.:
20009
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.590
Gnomad AMI
AF:
0.563
Gnomad AMR
AF:
0.501
Gnomad ASJ
AF:
0.481
Gnomad EAS
AF:
0.376
Gnomad SAS
AF:
0.388
Gnomad FIN
AF:
0.568
Gnomad MID
AF:
0.472
Gnomad NFE
AF:
0.472
Gnomad OTH
AF:
0.484
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.509
AC:
77378
AN:
152070
Hom.:
20040
Cov.:
33
AF XY:
0.511
AC XY:
37989
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.590
Gnomad4 AMR
AF:
0.502
Gnomad4 ASJ
AF:
0.481
Gnomad4 EAS
AF:
0.376
Gnomad4 SAS
AF:
0.388
Gnomad4 FIN
AF:
0.568
Gnomad4 NFE
AF:
0.472
Gnomad4 OTH
AF:
0.481
Alfa
AF:
0.495
Hom.:
3821
Bravo
AF:
0.509
Asia WGS
AF:
0.404
AC:
1404
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
1.1
DANN
Benign
0.47

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

LitVar

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

Other links and lift over

dbSNP: rs7091540; hg19: chr10-131420276; API