rs11212570

chr11-108259985-G-Achr11-108259985-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.2466+910G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0741 in 149,010 control chromosomes in the GnomAD database, including 536 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 0.074 (536 hom., cov: 32)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4	c.2466+910G>A		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.2466+910G>A		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes AF: 0.0741 AC: 11044 AN: 148980 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0359

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0174

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0323

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0684

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

GnomAD4 genome AF: 0.0741 AC: 11044 AN: 149010 Hom.: 536 Cov.: 32 AF XY: 0.0715 AC XY: 5181 AN XY: 72496

Gnomad4 AFR AF: 0.0210

Gnomad4 AMR AF: 0.0750

Gnomad4 ASJ AF: 0.0359

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.0171

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0942 Hom.: 1100

Bravo AF: 0.0723

Asia WGS AF: 0.0750 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.020
Dann	Benign	0.19

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: rs11212570; hg19: chr11-108130712; COSMIC: COSV53777925;