chr11-108279480-CT-C

Variant summary

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

The NM_000051.4(ATM):​c.3285-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,573,082 control chromosomes in the GnomAD database, including 14,912 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1202 hom., cov: 31)
Exomes 𝑓: 0.13 ( 13710 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: 0.508
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 11-108279480-CT-C is Benign according to our data. Variant chr11-108279480-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 181857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108279480-CT-C is described in Lovd as [Benign]. Variant chr11-108279480-CT-C is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATMNM_000051.4 linkc.3285-9delT intron_variant Intron 22 of 62 ENST00000675843.1 NP_000042.3 Q13315A0A024R3C7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATMENST00000675843.1 linkc.3285-10delT intron_variant Intron 22 of 62 NM_000051.4 ENSP00000501606.1 Q13315

Frequencies

GnomAD3 genomes
AF:
0.106
AC:
16172
AN:
152030
Hom.:
1202
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0239
Gnomad AMI
AF:
0.332
Gnomad AMR
AF:
0.0918
Gnomad ASJ
AF:
0.144
Gnomad EAS
AF:
0.00788
Gnomad SAS
AF:
0.0753
Gnomad FIN
AF:
0.237
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.145
Gnomad OTH
AF:
0.105
GnomAD3 exomes
AF:
0.113
AC:
25710
AN:
227570
Hom.:
1853
AF XY:
0.115
AC XY:
14159
AN XY:
122668
show subpopulations
Gnomad AFR exome
AF:
0.0227
Gnomad AMR exome
AF:
0.0614
Gnomad ASJ exome
AF:
0.130
Gnomad EAS exome
AF:
0.00632
Gnomad SAS exome
AF:
0.0768
Gnomad FIN exome
AF:
0.241
Gnomad NFE exome
AF:
0.143
Gnomad OTH exome
AF:
0.124
GnomAD4 exome
AF:
0.132
AC:
187000
AN:
1420934
Hom.:
13710
Cov.:
21
AF XY:
0.131
AC XY:
92695
AN XY:
707534
show subpopulations
Gnomad4 AFR exome
AF:
0.0209
Gnomad4 AMR exome
AF:
0.0646
Gnomad4 ASJ exome
AF:
0.134
Gnomad4 EAS exome
AF:
0.00314
Gnomad4 SAS exome
AF:
0.0772
Gnomad4 FIN exome
AF:
0.235
Gnomad4 NFE exome
AF:
0.142
Gnomad4 OTH exome
AF:
0.120
GnomAD4 genome
AF:
0.106
AC:
16175
AN:
152148
Hom.:
1202
Cov.:
31
AF XY:
0.108
AC XY:
8065
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0239
Gnomad4 AMR
AF:
0.0916
Gnomad4 ASJ
AF:
0.144
Gnomad4 EAS
AF:
0.00790
Gnomad4 SAS
AF:
0.0762
Gnomad4 FIN
AF:
0.237
Gnomad4 NFE
AF:
0.145
Gnomad4 OTH
AF:
0.103
Alfa
AF:
0.125
Hom.:
256
Bravo
AF:
0.0928
Asia WGS
AF:
0.0370
AC:
128
AN:
3474

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:20
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:9
Mar 28, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

May 16, 2017
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Oct 15, 2013
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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:4
Jul 14, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 04, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Oct 09, 2014
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not provided Benign:3
Nov 27, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Nov 03, 2021
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:2
Mar 31, 2015
Color Diagnostics, LLC DBA Color Health
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 12, 2015
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Familial cancer of breast Benign:1
May 14, 2024
Myriad Genetics, Inc.
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -

Hereditary breast ovarian cancer syndrome Benign:1
Apr 19, 2022
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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.

Other links and lift over

dbSNP: rs1799757; hg19: chr11-108150207; API