rs609261

chr11-108287407-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000051.4(ATM):c.3994-193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 386,940 control chromosomes in the GnomAD database, including 58,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21764 hom., cov: 31)
  • Exomes 𝑓: 0.55 (37020 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.481

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-108287407-T-C is Benign according to our data. Variant chr11-108287407-T-C is described in ClinVar as [Benign]. Clinvar id is 516633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.3994-193T>C		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.3994-193T>C		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79760 AN: 151846 Hom.: 21754 Cov.: 31

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.552 AC: 129709 AN: 234976 Hom.: 37020 Cov.: 3 AF XY: 0.557 AC XY: 68660 AN XY: 123172

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.618

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.525 AC: 79794 AN: 151964 Hom.: 21764 Cov.: 31 AF XY: 0.533 AC XY: 39611 AN XY: 74264

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.641

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.560

Alfa AF: 0.571 Hom.: 48635

Bravo AF: 0.514

Asia WGS AF: 0.550 AC: 1913 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 15, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Ataxia-telangiectasia syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.5
Dann	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs609261; hg19: chr11-108158134;