rs228592

Positions:

• chr11-108252462-C-A
• chr11-108252462-C-G
• chr11-108252462-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000051.4(ATM):​c.1803-355C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,872 control chromosomes in the GnomAD database, including 23,128 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 0.55 (23128 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4	c.1803-355C>A		intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.1803-355C>A		intron_variant			NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83003 AN: 151754 Hom.: 23114 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.578

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

GnomAD4 genome AF: 0.547 AC: 83046 AN: 151872 Hom.: 23128 Cov.: 32 AF XY: 0.554 AC XY: 41131 AN XY: 74232

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.579

Alfa AF: 0.545 Hom.: 3326

Bravo AF: 0.539

Asia WGS AF: 0.575 AC: 1997 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 25

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

Publications

LitVar

Other links and lift over

dbSNP: rs228592; hg19: chr11-108123189;