rs10734088

Variant names:

• chr10-129699451-G-A
• rs10734088
• NM_002412.5:c.126-8444G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-129699451-G-A
• chr10-129699451-G-C

Variant summary

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

The NM_002412.5(MGMT):​c.126-8444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,820 control chromosomes in the GnomAD database, including 27,909 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 0.60 (27909 hom., cov: 31)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• 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]

ENSG00000237224 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGMT	NM_002412.5	c.126-8444G>A		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.126-8444G>A		intron_variant	Intron 2 of 4		NM_002412.5	ENSP00000498729.1
MGMT	ENST00000306010.8	c.219-8444G>A		intron_variant	Intron 2 of 4	1		ENSP00000302111.7
ENSG00000237224	ENST00000598332.2	n.304+1428C>T		intron_variant	Intron 1 of 1	5
ENSG00000237224	ENST00000628250.1	n.300+1428C>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90824 AN: 151702 Hom.: 27909 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.715

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.598 AC: 90848 AN: 151820 Hom.: 27909 Cov.: 31 AF XY: 0.600 AC XY: 44479 AN XY: 74192

African (AFR) AF: 0.470 AC: 19437 AN: 41340

American (AMR) AF: 0.505 AC: 7707 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3468

East Asian (EAS) AF: 0.707 AC: 3643 AN: 5152

South Asian (SAS) AF: 0.714 AC: 3429 AN: 4802

European-Finnish (FIN) AF: 0.703 AC: 7405 AN: 10538

Middle Eastern (MID) AF: 0.621 AC: 180 AN: 290

European-Non Finnish (NFE) AF: 0.663 AC: 45061 AN: 67950

Other (OTH) AF: 0.595 AC: 1254 AN: 2106

Alfa AF: 0.613 Hom.: 11318

Bravo AF: 0.572

Asia WGS AF: 0.670 AC: 2328 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	1.9
DANN	Benign	0.65
PhyloP100		-0.10
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: rs10734088; hg19: chr10-131497715;