11-108340685-T-G

Variant names:

• chr11-108340685-T-G
• rs227070
• NM_000051.4:c.8269-2537T>G

Variant summary

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

The NM_000051.4(ATM):​c.8269-2537T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,006 control chromosomes in the GnomAD database, including 29,588 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 0.62 (29588 hom., cov: 31)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 9 publications found

Genes affected

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.8269-2537T>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8269-2537T>G		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-31614A>C		intron	N/A	NP_001317297.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.8269-2537T>G		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.8269-2537T>G		intron	N/A	ENSP00000388058.2
	C11orf65	ENST00000615746.4	TSL:1	c.*1197-5393A>C		intron	N/A	ENSP00000483537.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94278 AN: 151888 Hom.: 29558 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.621 AC: 94355 AN: 152006 Hom.: 29588 Cov.: 31 AF XY: 0.625 AC XY: 46435 AN XY: 74294

African (AFR) AF: 0.686 AC: 28448 AN: 41478

American (AMR) AF: 0.662 AC: 10120 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2324 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2303 AN: 5150

South Asian (SAS) AF: 0.653 AC: 3151 AN: 4828

European-Finnish (FIN) AF: 0.630 AC: 6645 AN: 10552

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39218 AN: 67932

Other (OTH) AF: 0.631 AC: 1332 AN: 2110

Alfa AF: 0.606 Hom.: 4226

Bravo AF: 0.623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.86
DANN	Benign	0.63
PhyloP100		-0.43
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: rs227070; hg19: chr11-108211412;