dbSNP rs7068256: MGMT:c.126-7768G>A (chr10-129700127-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406

Publications

5 publications found

Variant links:

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]

MGMT links:

ENSG00000237224 (HGNC:):

ENSG00000237224 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Sel.	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	P16455

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MGMT	ENST00000651593.1	MANE Select	c.126-7768G>A	intron	N/A	ENSP00000498729.1	P16455
MGMT	ENST00000306010.8	TSL:1	c.219-7768G>A	intron	N/A	ENSP00000302111.7	B4DEE8
MGMT	ENST00000897068.1		c.126-7768G>A	intron	N/A	ENSP00000567127.1

Frequencies

GnomAD3 genomes

AF:

0.655

AC:

99329

AN:

151732

Hom.:

34545

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.654

AC:

99342

AN:

151850

Hom.:

34540

Cov.:

AF XY:

0.654

AC XY:

48530

AN XY:

74190

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1554

3108

4661

6215

7769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.70

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over