10-129692156-G-C

Variant names:

• chr10-129692156-G-C
• rs10829618
• NM_002412.5:c.126-15739G>C

Variant summary

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

The NM_002412.5(MGMT):​c.126-15739G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,118 control chromosomes in the GnomAD database, including 49,025 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 0.80 (49025 hom., cov: 32)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.704
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 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.126-15739G>C		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.126-15739G>C		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.219-15739G>C		intron	N/A	ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121733 AN: 152000 Hom.: 48986 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.801 AC: 121824 AN: 152118 Hom.: 49025 Cov.: 32 AF XY: 0.798 AC XY: 59310 AN XY: 74358

African (AFR) AF: 0.882 AC: 36627 AN: 41536

American (AMR) AF: 0.732 AC: 11179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.760 AC: 2634 AN: 3468

East Asian (EAS) AF: 0.701 AC: 3591 AN: 5120

South Asian (SAS) AF: 0.807 AC: 3893 AN: 4822

European-Finnish (FIN) AF: 0.754 AC: 7988 AN: 10596

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53397 AN: 67982

Other (OTH) AF: 0.789 AC: 1665 AN: 2110

Alfa AF: 0.793 Hom.: 5625

Bravo AF: 0.797

Asia WGS AF: 0.737 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.61
PhyloP100		0.70
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: rs10829618; hg19: chr10-131490420;