rs7071825

Positions:

• chr10-129760387-G-A
• chr10-129760387-G-T

Variant summary

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

The NM_002412.5(MGMT):​c.414+1046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,170 control chromosomes in the GnomAD database, including 32,902 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 (32902 hom., cov: 34)
• Consequence: MGMT NM_002412.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGMT	NM_002412.5	c.414+1046G>A		intron_variant		ENST00000651593.1	NP_002403.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGMT	ENST00000651593.1	c.414+1046G>A		intron_variant			NM_002412.5	ENSP00000498729	P1
MGMT	ENST00000306010.8	c.507+1046G>A		intron_variant		1		ENSP00000302111

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98603 AN: 152050 Hom.: 32842 Cov.: 34

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.649 AC: 98723 AN: 152170 Hom.: 32902 Cov.: 34 AF XY: 0.651 AC XY: 48391 AN XY: 74376

Gnomad4 AFR AF: 0.803

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.657

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.589

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.620

Alfa AF: 0.581 Hom.: 25528

Bravo AF: 0.663

Asia WGS AF: 0.649 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0020
DANN	Benign	0.63

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: rs7071825; hg19: chr10-131558651;