rs7068256

Variant names:

• chr10-129700127-G-A
• rs7068256
• NM_002412.5:c.126-7768G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-129700127-G-A
• chr10-129700127-G-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.126-7768G>A 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 151,854 control chromosomes in the GnomAD database, including 34,541 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 (34540 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• 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]

ENSG00000237224 (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 (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.126-7768G>A		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.126-7768G>A		intron	N/A	ENSP00000498729.1
	MGMT	ENST00000306010.8	TSL:1	c.219-7768G>A		intron	N/A	ENSP00000302111.7
	ENSG00000237224	ENST00000598332.2	TSL:5	n.304+752C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99329 AN: 151732 Hom.: 34545 Cov.: 31

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.654 AC: 99342 AN: 151850 Hom.: 34540 Cov.: 31 AF XY: 0.654 AC XY: 48530 AN XY: 74190

African (AFR) AF: 0.401 AC: 16586 AN: 41376

American (AMR) AF: 0.676 AC: 10325 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2590 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3283 AN: 5154

South Asian (SAS) AF: 0.765 AC: 3678 AN: 4808

European-Finnish (FIN) AF: 0.737 AC: 7755 AN: 10520

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

European-Non Finnish (NFE) AF: 0.779 AC: 52915 AN: 67948

Other (OTH) AF: 0.670 AC: 1412 AN: 2106

Alfa AF: 0.744 Hom.: 19357

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	-0.89
CADD	Benign	0.96
DANN	Benign	0.70
PhyloP100		-0.41
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: rs7068256; hg19: chr10-131498391;