rs228590

chr11-108225414-A-Gchr11-108225414-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000051.4(ATM):c.-30-2181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,104 control chromosomes in the GnomAD database, including 21,812 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 (21800 hom., cov: 32)
  • Exomes 𝑓: 0.65 (12 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4	c.-30-2181A>G		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.-30-2181A>G		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79795 AN: 151932 Hom.: 21789 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.648 AC: 35 AN: 54 Hom.: 12 Cov.: 0 AF XY: 0.632 AC XY: 24 AN XY: 38

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.750

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.765

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.525 AC: 79829 AN: 152050 Hom.: 21800 Cov.: 32 AF XY: 0.534 AC XY: 39649 AN XY: 74316

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.560

Alfa AF: 0.521 Hom.: 3544

Bravo AF: 0.514

Asia WGS AF: 0.569 AC: 1980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.4
Dann	Benign	0.86

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: rs228590; hg19: chr11-108096141;