10-129716206-C-T

Variant names:

• chr10-129716206-C-T
• rs11016887
• NM_002412.5:c.274+8163C>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.274+8163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,104 control chromosomes in the GnomAD database, including 8,866 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 0.30 (8866 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• 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]

LOC105378560 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 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.274+8163C>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.274+8163C>T		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.367+8163C>T		intron	N/A	ENSP00000302111.7
	MGMT	ENST00000462672.1	TSL:3	n.520+602C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46122 AN: 151986 Hom.: 8834 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.304 AC: 46212 AN: 152104 Hom.: 8866 Cov.: 33 AF XY: 0.310 AC XY: 23026 AN XY: 74364

African (AFR) AF: 0.526 AC: 21841 AN: 41490

American (AMR) AF: 0.271 AC: 4135 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3468

East Asian (EAS) AF: 0.479 AC: 2471 AN: 5160

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4824

European-Finnish (FIN) AF: 0.266 AC: 2811 AN: 10576

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11949 AN: 67986

Other (OTH) AF: 0.311 AC: 658 AN: 2114

Alfa AF: 0.230 Hom.: 10156

Bravo AF: 0.315

Asia WGS AF: 0.419 AC: 1456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-0.33
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: rs11016887; hg19: chr10-131514470;