chr10-129629305-C-T

Variant names:

• chr10-129629305-C-T
• rs531572
• NM_002412.5:c.126-78590C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002412.5(MGMT):​c.126-78590C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,094 control chromosomes in the GnomAD database, including 15,988 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 0.45 (15988 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374
• Publications: 23 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002412.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	NM_002412.5	MANE Select	c.126-78590C>T		intron	N/A	NP_002403.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	ENST00000651593.1	MANE Select	c.126-78590C>T		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.219-78590C>T		intron	N/A	ENSP00000302111.7
	MGMT	ENST00000897068.1		c.126-78590C>T		intron	N/A	ENSP00000567127.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68746 AN: 151976 Hom.: 15981 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.452 AC: 68782 AN: 152094 Hom.: 15988 Cov.: 33 AF XY: 0.450 AC XY: 33451 AN XY: 74318

African (AFR) AF: 0.357 AC: 14824 AN: 41478

American (AMR) AF: 0.458 AC: 7003 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3470

East Asian (EAS) AF: 0.624 AC: 3223 AN: 5162

South Asian (SAS) AF: 0.551 AC: 2656 AN: 4816

European-Finnish (FIN) AF: 0.409 AC: 4325 AN: 10582

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33467 AN: 67990

Other (OTH) AF: 0.476 AC: 1006 AN: 2114

Alfa AF: 0.481 Hom.: 11277

Bravo AF: 0.452

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.65
PhyloP100		-0.37
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

Other links and lift over

dbSNP: rs531572; hg19: chr10-131427569;