rs1762429

Positions:

• chr10-129475443-C-T

Variant summary

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

The NM_002412.5(MGMT):​c.-13+8147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,972 control chromosomes in the GnomAD database, including 21,441 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 0.50 (21441 hom., cov: 32)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199

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]

MGMT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGMT	NM_002412.5	c.-13+8147C>T		intron_variant		ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.-13+8147C>T		intron_variant			NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.81+8147C>T		intron_variant		1		ENSP00000302111.7
MGMT	ENST00000482547.1	n.35+8147C>T		intron_variant		2
MGMT	ENST00000482653.1	n.68+8147C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75891 AN: 151856 Hom.: 21446 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.499 AC: 75890 AN: 151972 Hom.: 21441 Cov.: 32 AF XY: 0.508 AC XY: 37703 AN XY: 74248

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.632

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.550

Alfa AF: 0.583 Hom.: 25545

Bravo AF: 0.481

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.76

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: rs1762429; hg19: chr10-131273707;