rs3092991

Variant names:

• chr11-108269789-A-G
• rs3092991
• NM_000051.4:c.2838+1180A>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.2838+1180A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,242 control chromosomes in the GnomAD database, including 1,224 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 0.11 (1224 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235
• Publications: 18 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):

• ATM-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hereditary breast carcinoma

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

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

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

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary nonpolyposis colon cancer

  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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.2838+1180A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.2838+1180A>G		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.2838+1180A>G		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.2838+1180A>G		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000531525.3	TSL:1	c.2838+1180A>G		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16333 AN: 152124 Hom.: 1224 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.144

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.107 AC: 16336 AN: 152242 Hom.: 1224 Cov.: 32 AF XY: 0.109 AC XY: 8148 AN XY: 74420

African (AFR) AF: 0.0257 AC: 1070 AN: 41558

American (AMR) AF: 0.0921 AC: 1408 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 498 AN: 3470

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5184

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4826

European-Finnish (FIN) AF: 0.240 AC: 2536 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9870 AN: 68012

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.108 Hom.: 185

Bravo AF: 0.0938

Asia WGS AF: 0.0370 AC: 130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		0.23
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: rs3092991; hg19: chr11-108140516;