rs11813056

Variant names:

• chr10-129530382-T-C
• rs11813056
• NM_002412.5:c.-12-5859T>C

Variant summary

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

The NM_002412.5(MGMT):​c.-12-5859T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,204 control chromosomes in the GnomAD database, including 2,818 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 0.18 (2818 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 4 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 = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.-12-5859T>C		intron_variant	Intron 1 of 4	ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.-12-5859T>C		intron_variant	Intron 1 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.82-5859T>C		intron_variant	Intron 1 of 4	1		ENSP00000302111.7
MGMT	ENST00000482547.1	n.36-5859T>C		intron_variant	Intron 1 of 1	2
MGMT	ENST00000482653.1	n.69-5859T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27496 AN: 152086 Hom.: 2812 Cov.: 33

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.181 AC: 27524 AN: 152204 Hom.: 2818 Cov.: 33 AF XY: 0.176 AC XY: 13111 AN XY: 74404

African (AFR) AF: 0.261 AC: 10836 AN: 41506

American (AMR) AF: 0.143 AC: 2179 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 497 AN: 3468

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5190

South Asian (SAS) AF: 0.0960 AC: 463 AN: 4824

European-Finnish (FIN) AF: 0.150 AC: 1595 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11354 AN: 68010

Other (OTH) AF: 0.174 AC: 368 AN: 2114

Alfa AF: 0.184 Hom.: 1580

Bravo AF: 0.184

Asia WGS AF: 0.0730 AC: 256 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	0.51
DANN	Benign	0.47
PhyloP100		-2.4
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: rs11813056; hg19: chr10-131328646;