10-129691518-A-G

Variant names:

• chr10-129691518-A-G
• rs11016879
• NM_002412.5:c.126-16377A>G

Variant summary

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

The NM_002412.5(MGMT):​c.126-16377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,152 control chromosomes in the GnomAD database, including 33,759 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 0.66 (33759 hom., cov: 34)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 11 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	NM_002412.5	MANE Select	c.126-16377A>G		intron	N/A	NP_002403.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	ENST00000651593.1	MANE Select	c.126-16377A>G		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.219-16377A>G		intron	N/A	ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100234 AN: 152034 Hom.: 33710 Cov.: 34

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.659 AC: 100336 AN: 152152 Hom.: 33759 Cov.: 34 AF XY: 0.656 AC XY: 48773 AN XY: 74376

African (AFR) AF: 0.797 AC: 33113 AN: 41534

American (AMR) AF: 0.605 AC: 9252 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2214 AN: 3470

East Asian (EAS) AF: 0.603 AC: 3098 AN: 5136

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4824

European-Finnish (FIN) AF: 0.531 AC: 5619 AN: 10580

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.620 AC: 42137 AN: 67998

Other (OTH) AF: 0.630 AC: 1329 AN: 2110

Alfa AF: 0.627 Hom.: 36177

Bravo AF: 0.670

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.20
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: rs11016879; hg19: chr10-131489782;