10-129764887-T-G

Variant names:

• chr10-129764887-T-G
• rs3793912
• NM_002412.5:c.415-1901T>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.415-1901T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,898 control chromosomes in the GnomAD database, including 33,920 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 (33920 hom., cov: 31)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.488
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.415-1901T>G		intron_variant	Intron 4 of 4	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.415-1901T>G		intron_variant	Intron 4 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.508-1901T>G		intron_variant	Intron 4 of 4	1		ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99789 AN: 151778 Hom.: 33858 Cov.: 31

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.658 AC: 99911 AN: 151898 Hom.: 33920 Cov.: 31 AF XY: 0.659 AC XY: 48941 AN XY: 74216

African (AFR) AF: 0.831 AC: 34449 AN: 41478

American (AMR) AF: 0.693 AC: 10569 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2155 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3410 AN: 5126

South Asian (SAS) AF: 0.630 AC: 3032 AN: 4812

European-Finnish (FIN) AF: 0.589 AC: 6215 AN: 10550

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

European-Non Finnish (NFE) AF: 0.560 AC: 37999 AN: 67890

Other (OTH) AF: 0.623 AC: 1317 AN: 2114

Alfa AF: 0.589 Hom.: 87764

Bravo AF: 0.674

Asia WGS AF: 0.655 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.70
DANN	Benign	0.21
PhyloP100		-0.49
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: rs3793912; hg19: chr10-131563151;