rs2053139

chr10-129710868-T-Cchr10-129710868-T-G

Variant summary

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

The NM_002412.5(MGMT):c.274+2825T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.345 in 152,126 control chromosomes in the GnomAD database, including 9,275 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 0.35 (9275 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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]

LOC105378560 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGMT	NM_002412.5	c.274+2825T>C		intron_variant		ENST00000651593.1
LOC105378560	XR_946467.3	n.2819T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGMT	ENST00000651593.1	c.274+2825T>C		intron_variant			NM_002412.5	P1
MGMT	ENST00000306010.8	c.367+2825T>C		intron_variant		1
MGMT	ENST00000462672.1	n.435+2825T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52528 AN: 152008 Hom.: 9271 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.345 AC: 52551 AN: 152126 Hom.: 9275 Cov.: 33 AF XY: 0.345 AC XY: 25660 AN XY: 74382

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.337

Alfa AF: 0.331 Hom.: 7767

Bravo AF: 0.343

Asia WGS AF: 0.485 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.55
Dann	Benign	0.55

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: rs2053139; hg19: chr10-131509132;