10-129699994-C-T

Variant names:

• chr10-129699994-C-T
• rs7069143
• NM_002412.5:c.126-7901C>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.126-7901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 151,908 control chromosomes in the GnomAD database, including 11,387 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 0.37 (11387 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 4 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]

ENSG00000237224 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.126-7901C>T		intron_variant	Intron 2 of 4	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.126-7901C>T		intron_variant	Intron 2 of 4		NM_002412.5	ENSP00000498729.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56141 AN: 151790 Hom.: 11393 Cov.: 33

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.370 AC: 56159 AN: 151908 Hom.: 11387 Cov.: 33 AF XY: 0.369 AC XY: 27397 AN XY: 74218

African (AFR) AF: 0.210 AC: 8698 AN: 41434

American (AMR) AF: 0.322 AC: 4919 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3470

East Asian (EAS) AF: 0.331 AC: 1700 AN: 5142

South Asian (SAS) AF: 0.407 AC: 1957 AN: 4810

European-Finnish (FIN) AF: 0.499 AC: 5242 AN: 10502

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30889 AN: 67968

Other (OTH) AF: 0.362 AC: 766 AN: 2114

Alfa AF: 0.398 Hom.: 1683

Bravo AF: 0.347

Asia WGS AF: 0.345 AC: 1201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.56
PhyloP100		-0.16
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: rs7069143; hg19: chr10-131498258;