rs511361

Variant names:

• chr10-129566788-C-T
• rs511361
• NM_002412.5:c.125+30411C>T

Variant summary

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

The NM_002412.5(MGMT):​c.125+30411C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,950 control chromosomes in the GnomAD database, including 12,800 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 0.40 (12800 hom., cov: 31)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.125+30411C>T		intron_variant	Intron 2 of 4	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.125+30411C>T		intron_variant	Intron 2 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.218+30411C>T		intron_variant	Intron 2 of 4	1		ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60717 AN: 151832 Hom.: 12800 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.400 AC: 60728 AN: 151950 Hom.: 12800 Cov.: 31 AF XY: 0.400 AC XY: 29706 AN XY: 74224

African (AFR) AF: 0.267 AC: 11071 AN: 41456

American (AMR) AF: 0.437 AC: 6672 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1637 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3137 AN: 5112

South Asian (SAS) AF: 0.538 AC: 2591 AN: 4814

European-Finnish (FIN) AF: 0.370 AC: 3911 AN: 10564

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.445 AC: 30253 AN: 67942

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.419 Hom.: 2283

Bravo AF: 0.398

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.65
DANN	Benign	0.50
PhyloP100		-1.5
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: rs511361; hg19: chr10-131365052;