rs228597

chr11-108236282-G-Achr11-108236282-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4	c.496+448G>A		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.496+448G>A		intron_variant			NM_000051.4	P1

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

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.469

Gnomad4 SAS exome AF: 0.662

Gnomad4 FIN exome AF: 0.624

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.582

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

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.568

Alfa AF: 0.546 Hom.: 2855

Bravo AF: 0.523

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.7
Dann	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs228597; hg19: chr11-108107009;