rs7068306

Variant names:

• chr10-129671773-C-G
• rs7068306
• NM_002412.5:c.126-36122C>G

Variant summary

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

The NM_002412.5(MGMT):​c.126-36122C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,094 control chromosomes in the GnomAD database, including 8,228 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 0.32 (8228 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.126-36122C>G		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.126-36122C>G		intron_variant	Intron 2 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.219-36122C>G		intron_variant	Intron 2 of 4	1		ENSP00000302111.7

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48617 AN: 151972 Hom.: 8223 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.320 AC: 48651 AN: 152094 Hom.: 8228 Cov.: 33 AF XY: 0.325 AC XY: 24167 AN XY: 74328

African (AFR) AF: 0.223 AC: 9238 AN: 41490

American (AMR) AF: 0.353 AC: 5386 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1128 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2488 AN: 5158

South Asian (SAS) AF: 0.368 AC: 1776 AN: 4826

European-Finnish (FIN) AF: 0.428 AC: 4519 AN: 10564

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22875 AN: 67994

Other (OTH) AF: 0.339 AC: 715 AN: 2112

Alfa AF: 0.329 Hom.: 1049

Bravo AF: 0.311

Asia WGS AF: 0.446 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.34
PhyloP100		-0.27
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: rs7068306; hg19: chr10-131470037;