rs582157

chr11-108290475-T-A

Variant summary

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

The NM_000051.4(ATM):c.4436+674T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 150,666 control chromosomes in the GnomAD database, including 22,172 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 0.54 (22156 hom., cov: 26)
  • Exomes 𝑓: 0.57 (16 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.07

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=-1.14).
• 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.4436+674T>A		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.4436+674T>A		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 80624 AN: 150472 Hom.: 22146 Cov.: 26

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.569

GnomAD4 exome AF: 0.575 AC: 46 AN: 80 Hom.: 16 Cov.: 0 AF XY: 0.545 AC XY: 36 AN XY: 66

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.661

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.536 AC: 80663 AN: 150586 Hom.: 22156 Cov.: 26 AF XY: 0.543 AC XY: 39914 AN XY: 73528

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.570

Alfa AF: 0.548 Hom.: 2863

Bravo AF: 0.525

Asia WGS AF: 0.551 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.0040
Dann	Benign	0.055

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: rs582157; hg19: chr11-108161202; COSMIC: COSV53736463; COSMIC: COSV53736463;