chr10-129466472-G-A

Variant names:

• chr10-129466472-G-A
• rs61859810
• ENST00000735692.1:n.95+1094C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000735692.1(ENSG00000296036):​n.95+1094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 152,206 control chromosomes in the GnomAD database, including 4 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 0.0074 (4 hom., cov: 32)
• Consequence: ENSG00000296036 ENST00000735692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 3 publications found

Genes affected

ENSG00000296036 (HGNC:):

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000735692.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000296036	ENST00000735692.1		n.95+1094C>T		intron	N/A
	MGMT	ENST00000932196.1		c.-374G>A		upstream_gene	N/A	ENSP00000602255.1

Frequencies

GnomAD3 genomes AF: 0.00740 AC: 1125 AN: 152088 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.00767

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.00739 AC: 1125 AN: 152206 Hom.: 4 Cov.: 32 AF XY: 0.00714 AC XY: 531 AN XY: 74400

African (AFR) AF: 0.00272 AC: 113 AN: 41550

American (AMR) AF: 0.00981 AC: 150 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5156

South Asian (SAS) AF: 0.00768 AC: 37 AN: 4818

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0109 AC: 739 AN: 68000

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00796

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.6
DANN	Benign	0.60
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61859810; hg19: chr10-131264736;