rs10764899

Variant names:

• chr10-129698898-C-T
• rs10764899
• NM_002412.5:c.126-8997C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002412.5(MGMT):​c.126-8997C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,136 control chromosomes in the GnomAD database, including 34,628 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 0.65 (34628 hom., cov: 34)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 1 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]

ENSG00000237224 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002412.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	NM_002412.5	MANE Select	c.126-8997C>T		intron	N/A	NP_002403.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGMT	ENST00000651593.1	MANE Select	c.126-8997C>T		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.219-8997C>T		intron	N/A	ENSP00000302111.7
	ENSG00000237224	ENST00000598332.2	TSL:5	n.304+1981G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99527 AN: 152018 Hom.: 34632 Cov.: 34

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.654 AC: 99541 AN: 152136 Hom.: 34628 Cov.: 34 AF XY: 0.654 AC XY: 48676 AN XY: 74376

African (AFR) AF: 0.401 AC: 16632 AN: 41490

American (AMR) AF: 0.677 AC: 10351 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2591 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3296 AN: 5168

South Asian (SAS) AF: 0.765 AC: 3682 AN: 4814

European-Finnish (FIN) AF: 0.738 AC: 7804 AN: 10574

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52970 AN: 68004

Other (OTH) AF: 0.670 AC: 1417 AN: 2116

Alfa AF: 0.688 Hom.: 5731

Bravo AF: 0.631

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.74
PhyloP100		3.2
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: rs10764899; hg19: chr10-131497162;