Variant 11-108354756-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000051.4(ATM):c.8787-55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,417,564 control chromosomes in the GnomAD database, including 227,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22541 hom., cov: 33)

Exomes 𝑓: 0.57 ( 204477 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.70

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:

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

C11orf65 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 11-108354756-C-T is Benign according to our data. Variant chr11-108354756-C-T is described in ClinVar as [Benign]. Clinvar id is 1177616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108354756-C-T is described in Lovd as [Benign].

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 linkuse as main transcript	c.8787-55C>T		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.8787-55C>T		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81656

AN:

151924

Hom.:

22528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.649

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.568

GnomAD4 exome

AF:

0.566

AC:

716048

AN:

1265522

Hom.:

204477

AF XY:

0.570

AC XY:

365143

AN XY:

640216

show subpopulations

Gnomad4 AFR exome

AF:

0.412

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.614

Gnomad4 EAS exome

AF:

0.459

Gnomad4 SAS exome

AF:

0.645

Gnomad4 FIN exome

AF:

0.626

Gnomad4 NFE exome

AF:

0.559

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.537

AC:

81697

AN:

152042

Hom.:

22541

Cov.:

AF XY:

0.545

AC XY:

40516

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.640

Gnomad4 EAS

AF:

0.436

Gnomad4 SAS

AF:

0.650

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.569

Gnomad4 OTH

AF:

0.569

Alfa

AF:

0.413

Hom.:

1109

Bravo

AF:

0.529

Asia WGS

AF:

0.572

AC:

1990

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -

Ataxia-telangiectasia syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.13

DANN

Benign

0.65

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