chr11-108236933-G-A

Variant names:

• chr11-108236933-G-A
• rs228599
• NM_000051.4:c.496+1099G>A

Variant summary

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

The NM_000051.4(ATM):​c.496+1099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,028 control chromosomes in the GnomAD database, including 29,566 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 (29566 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 11 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]

ATM Gene-Disease associations (from GenCC):

• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• ataxia telangiectasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• prostate cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.496+1099G>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.496+1099G>A		intron	N/A	NP_001338763.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.496+1099G>A		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.496+1099G>A		intron	N/A	ENSP00000388058.2
	ATM	ENST00000531525.3	TSL:1	c.496+1099G>A		intron	N/A	ENSP00000434327.3

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94247 AN: 151910 Hom.: 29535 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.620 AC: 94324 AN: 152028 Hom.: 29566 Cov.: 32 AF XY: 0.625 AC XY: 46447 AN XY: 74318

African (AFR) AF: 0.686 AC: 28428 AN: 41464

American (AMR) AF: 0.662 AC: 10121 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2325 AN: 3466

East Asian (EAS) AF: 0.445 AC: 2305 AN: 5178

South Asian (SAS) AF: 0.654 AC: 3149 AN: 4816

European-Finnish (FIN) AF: 0.631 AC: 6659 AN: 10552

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39191 AN: 67944

Other (OTH) AF: 0.630 AC: 1333 AN: 2116

Alfa AF: 0.594 Hom.: 3335

Bravo AF: 0.623

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.28
PhyloP100		-0.24
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: rs228599; hg19: chr11-108107660;