chr10-129676210-G-A

Position:

• chr10-129676210-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002412.5(MGMT):​c.126-31685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,184 control chromosomes in the GnomAD database, including 1,973 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 0.15 (1973 hom., cov: 33)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGMT	NM_002412.5	c.126-31685G>A		intron_variant		ENST00000651593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MGMT	ENST00000651593.1	c.126-31685G>A		intron_variant			NM_002412.5	P1
MGMT	ENST00000306010.8	c.219-31685G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23352 AN: 152066 Hom.: 1970 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.154 AC: 23367 AN: 152184 Hom.: 1973 Cov.: 33 AF XY: 0.156 AC XY: 11611 AN XY: 74400

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.154

Alfa AF: 0.156 Hom.: 3390

Bravo AF: 0.140

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.37
DANN	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs7087131; hg19: chr10-131474474;