10-129731904-C-T

Variant names:

• chr10-129731904-C-T
• rs11016897
• NM_002412.5:c.274+23861C>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.274+23861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,892 control chromosomes in the GnomAD database, including 22,316 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 0.54 (22316 hom., cov: 31)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 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.274+23861C>T		intron	N/A	NP_002403.3	P16455

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	ENST00000651593.1	MANE Select	c.274+23861C>T		intron	N/A	ENSP00000498729.1	P16455
	MGMT	ENST00000306010.8	TSL:1	c.367+23861C>T		intron	N/A	ENSP00000302111.7	B4DEE8
	MGMT	ENST00000897068.1		c.274+23861C>T		intron	N/A	ENSP00000567127.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81482 AN: 151774 Hom.: 22287 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.537 AC: 81553 AN: 151892 Hom.: 22316 Cov.: 31 AF XY: 0.543 AC XY: 40311 AN XY: 74242

African (AFR) AF: 0.438 AC: 18134 AN: 41396

American (AMR) AF: 0.645 AC: 9855 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2345 AN: 3472

East Asian (EAS) AF: 0.648 AC: 3343 AN: 5156

South Asian (SAS) AF: 0.655 AC: 3142 AN: 4796

European-Finnish (FIN) AF: 0.534 AC: 5629 AN: 10550

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37227 AN: 67936

Other (OTH) AF: 0.541 AC: 1142 AN: 2112

Alfa AF: 0.536 Hom.: 3405

Bravo AF: 0.540

Asia WGS AF: 0.641 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.83
PhyloP100		0.0030
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: rs11016897; hg19: chr10-131530168;