Variant chr11-108287478-TC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000051.4(ATM):c.3994-121del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 603,396 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.556

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-108287478-TC-T is Benign according to our data. Variant chr11-108287478-TC-T is described in ClinVar as [Likely_benign]. Clinvar id is 254751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108287478-TC-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00586 (892/152268) while in subpopulation AFR AF= 0.0174 (724/41550). AF 95% confidence interval is 0.0164. There are 9 homozygotes in gnomad4. There are 410 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATM	NM_000051.4 linkuse as main transcript	c.3994-121del		intron_variant		ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 linkuse as main transcript	c.3994-121del		intron_variant			NM_000051.4	ENSP00000501606	P1

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

893

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.0133

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00573

GnomAD4 exome

AF:

0.00155

AC:

699

AN:

451128

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

365

AN XY:

240796

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.0145

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000427

Gnomad4 OTH exome

AF:

0.00291

GnomAD4 genome

AF:

0.00586

AC:

892

AN:

152268

Hom.:

Cov.:

AF XY:

0.00551

AC XY:

410

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.0133

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00567

Alfa

AF:

0.00484

Hom.:

Bravo

AF:

0.00715

Asia WGS

AF:

0.00144

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Ataxia-telangiectasia syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 25, 2019

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

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