rs2296675
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002412.5(MGMT):c.415-54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,523,598 control chromosomes in the GnomAD database, including 14,842 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 0.13 ( 1272 hom., cov: 34)
Exomes 𝑓: 0.14 ( 13570 hom. )
Consequence
MGMT
NM_002412.5 intron
NM_002412.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.53
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 made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MGMT | NM_002412.5 | c.415-54A>G | intron_variant | ENST00000651593.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MGMT | ENST00000651593.1 | c.415-54A>G | intron_variant | NM_002412.5 | P1 | ||||
MGMT | ENST00000306010.8 | c.508-54A>G | intron_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.127 AC: 19388AN: 152134Hom.: 1271 Cov.: 34
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GnomAD4 exome AF: 0.138 AC: 188660AN: 1371346Hom.: 13570 AF XY: 0.139 AC XY: 94339AN XY: 678666
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GnomAD4 genome ? AF: 0.127 AC: 19409AN: 152252Hom.: 1272 Cov.: 34 AF XY: 0.126 AC XY: 9375AN XY: 74444
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443
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3478
ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at