rs10764882

chr10-129508232-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002412.5(MGMT):c.-12-28009C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,920 control chromosomes in the GnomAD database, including 17,214 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 0.47 (17214 hom., cov: 32)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.626

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGMT	NM_002412.5	c.-12-28009C>G		intron_variant		ENST00000651593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGMT	ENST00000651593.1	c.-12-28009C>G		intron_variant			NM_002412.5	P1
MGMT	ENST00000306010.8	c.82-28009C>G		intron_variant		1
MGMT	ENST00000482547.1	n.36-28009C>G		intron_variant, non_coding_transcript_variant		2
MGMT	ENST00000482653.1	n.69-28009C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71321 AN: 151802 Hom.: 17214 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.470 AC: 71346 AN: 151920 Hom.: 17214 Cov.: 32 AF XY: 0.472 AC XY: 35027 AN XY: 74228

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.490

Alfa AF: 0.475 Hom.: 2180

Bravo AF: 0.462

Asia WGS AF: 0.581 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.4
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10764882; hg19: chr10-131306496;