rs228597

Variant names:

• chr11-108236282-G-A
• rs228597
• NM_000051.4:c.496+448G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-108236282-G-A
• chr11-108236282-G-T

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+448G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 206,194 control chromosomes in the GnomAD database, including 31,889 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 0.53 (22287 hom., cov: 33)
  • Exomes 𝑓: 0.59 (9602 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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]

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 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+448G>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.496+448G>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+448G>A		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.496+448G>A		intron	N/A	ENSP00000388058.2
	ATM	ENST00000531525.3	TSL:1	c.496+448G>A		intron	N/A	ENSP00000434327.3

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81010 AN: 151972 Hom.: 22275 Cov.: 33

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.567

GnomAD4 exome AF: 0.593 AC: 32059 AN: 54104 Hom.: 9602 Cov.: 0 AF XY: 0.600 AC XY: 17828 AN XY: 29710

African (AFR) AF: 0.440 AC: 333 AN: 756

American (AMR) AF: 0.654 AC: 1877 AN: 2872

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 784 AN: 1196

East Asian (EAS) AF: 0.469 AC: 973 AN: 2074

South Asian (SAS) AF: 0.662 AC: 6479 AN: 9788

European-Finnish (FIN) AF: 0.624 AC: 1332 AN: 2134

Middle Eastern (MID) AF: 0.737 AC: 140 AN: 190

European-Non Finnish (NFE) AF: 0.573 AC: 18584 AN: 32418

Other (OTH) AF: 0.582 AC: 1557 AN: 2676

GnomAD4 genome AF: 0.533 AC: 81046 AN: 152090 Hom.: 22287 Cov.: 33 AF XY: 0.541 AC XY: 40243 AN XY: 74326

African (AFR) AF: 0.401 AC: 16623 AN: 41498

American (AMR) AF: 0.622 AC: 9503 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2260 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2251 AN: 5170

South Asian (SAS) AF: 0.650 AC: 3136 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6655 AN: 10574

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38618 AN: 67966

Other (OTH) AF: 0.568 AC: 1199 AN: 2112

Alfa AF: 0.540 Hom.: 2916

Bravo AF: 0.523

Asia WGS AF: 0.572 AC: 1991 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	1.7
DANN	Benign	0.22
PhyloP100		-1.1
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: rs228597; hg19: chr11-108107009;