NM_002412.5:c.125+85635C>T

Variant names:

• chr10-129622012-C-T
• rs7091540
• NM_002412.5:c.125+85635C>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+85635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,070 control chromosomes in the GnomAD database, including 20,040 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 0.51 (20040 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• Publications: 3 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]

ENSG00000287466 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.125+85635C>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+85635C>T		intron_variant	Intron 2 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.218+85635C>T		intron_variant	Intron 2 of 4	1		ENSP00000302111.7
ENSG00000287466	ENST00000662900.1	n.2954G>A		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77298 AN: 151952 Hom.: 20009 Cov.: 33

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.509 AC: 77378 AN: 152070 Hom.: 20040 Cov.: 33 AF XY: 0.511 AC XY: 37989 AN XY: 74332

African (AFR) AF: 0.590 AC: 24465 AN: 41472

American (AMR) AF: 0.502 AC: 7666 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1668 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1946 AN: 5178

South Asian (SAS) AF: 0.388 AC: 1873 AN: 4822

European-Finnish (FIN) AF: 0.568 AC: 5997 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32095 AN: 67968

Other (OTH) AF: 0.481 AC: 1016 AN: 2112

Alfa AF: 0.498 Hom.: 3976

Bravo AF: 0.509

Asia WGS AF: 0.404 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.88
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: rs7091540; hg19: chr10-131420276;