Variant 11-108280970-AT-ATT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000051.4(ATM):c.3403-15dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,467,080 control chromosomes in the GnomAD database, including 934 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 640 hom., cov: 31)

Exomes 𝑓: 0.0064 ( 294 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.301

Variant links:

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]

ATM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-108280970-A-AT is Benign according to our data. Variant chr11-108280970-A-AT is described in ClinVar as [Benign]. Clinvar id is 235644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.3403-15dup		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.3403-15dup		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0724

AC:

7606

AN:

105064

Hom.:

631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.00191

Gnomad AMR

AF:

0.0465

Gnomad ASJ

AF:

0.00631

Gnomad EAS

AF:

0.00114

Gnomad SAS

AF:

0.00218

Gnomad FIN

AF:

0.000319

Gnomad MID

AF:

0.0208

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.0697

GnomAD3 exomes

AF:

0.0206

AC:

3217

AN:

156048

Hom.:

131

AF XY:

0.0162

AC XY:

1375

AN XY:

84626

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00118

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.000852

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.00645

AC:

8781

AN:

1361918

Hom.:

294

Cov.:

AF XY:

0.00566

AC XY:

3855

AN XY:

680542

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.00493

Gnomad4 EAS exome

AF:

0.000532

Gnomad4 SAS exome

AF:

0.000950

Gnomad4 FIN exome

AF:

0.000675

Gnomad4 NFE exome

AF:

0.00170

Gnomad4 OTH exome

AF:

0.0158

GnomAD4 genome

AF:

0.0727

AC:

7646

AN:

105162

Hom.:

640

Cov.:

AF XY:

0.0711

AC XY:

3607

AN XY:

50712

show subpopulations

Gnomad4 AFR

AF:

0.216

Gnomad4 AMR

AF:

0.0463

Gnomad4 ASJ

AF:

0.00631

Gnomad4 EAS

AF:

0.00115

Gnomad4 SAS

AF:

0.00182

Gnomad4 FIN

AF:

0.000319

Gnomad4 NFE

AF:

0.00191

Gnomad4 OTH

AF:

0.0691

Bravo

AF:

0.0582

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	Aug 15, 2023	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	May 05, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Ataxia-telangiectasia syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Breast and/or ovarian cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

May 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over