NM_002412.5:c.274+8555A>G

Variant names:

• chr10-129716598-A-G
• rs10764901
• NM_002412.5:c.274+8555A>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.274+8555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,056 control chromosomes in the GnomAD database, including 30,824 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 0.63 (30824 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725
• Publications: 8 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]

LOC105378560 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 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.274+8555A>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.274+8555A>G		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.367+8555A>G		intron	N/A	ENSP00000302111.7
	MGMT	ENST00000462672.1	TSL:3	n.520+994A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95135 AN: 151938 Hom.: 30807 Cov.: 33

Gnomad AFR AF: 0.481

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.626 AC: 95182 AN: 152056 Hom.: 30824 Cov.: 33 AF XY: 0.617 AC XY: 45902 AN XY: 74336

African (AFR) AF: 0.481 AC: 19925 AN: 41438

American (AMR) AF: 0.546 AC: 8335 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3331 AN: 5156

South Asian (SAS) AF: 0.663 AC: 3192 AN: 4812

European-Finnish (FIN) AF: 0.591 AC: 6253 AN: 10584

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49761 AN: 67998

Other (OTH) AF: 0.640 AC: 1354 AN: 2116

Alfa AF: 0.692 Hom.: 54933

Bravo AF: 0.613

Asia WGS AF: 0.669 AC: 2326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.024
DANN	Benign	0.21
PhyloP100		-0.72
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: rs10764901; hg19: chr10-131514862;