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GeneBe

rs1801516

Variant summary

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

The NM_000051.4(ATM):c.5557G>A(p.Asp1853Asn) variant causes a missense change. The variant allele was found at a frequency of 0.106 in 152020 control chromosomes in the gnomAD Genomes database, including 1205 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1853V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.11 ( 1205 hom., cov: 32)
Exomes 𝑓: 0.11 ( 2083 hom. )

Consequence

ATM
NM_000051.4 missense

Scores

1
3
14

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:21O:1

Conservation

PhyloP100: 5.93

Links

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=0.0014446676).
BP6
?
Variant 11-108304735-G-A is Benign according to our data. Variant chr11-108304735-G-A is described in ClinVar as [Benign]. Clinvar id is 128458.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108304735-G-A is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATMNM_000051.4 linkuse as main transcriptc.5557G>A p.Asp1853Asn missense_variant 37/63 ENST00000675843.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATMENST00000675843.1 linkuse as main transcriptc.5557G>A p.Asp1853Asn missense_variant 37/63 NM_000051.4 P1

Frequencies

GnomAD3 genomes
AF:
0.106
AC:
16174
AN:
152020
Hom.:
1205
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0240
Gnomad AMI
AF:
0.332
Gnomad AMR
AF:
0.0907
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.00789
Gnomad SAS
AF:
0.0749
Gnomad FIN
AF:
0.238
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.145
Gnomad OTH
AF:
0.105
GnomAD3 exomes
AF:
0.114
AC:
28505
AN:
250874
Hom.:
2083
AF XY:
0.116
AC XY:
15745
AN XY:
135594
show subpopulations
Gnomad AFR exome
AF:
0.0226
Gnomad AMR exome
AF:
0.0612
Gnomad ASJ exome
AF:
0.129
Gnomad EAS exome
AF:
0.00632
Gnomad SAS exome
AF:
0.0772
Gnomad FIN exome
AF:
0.242
Gnomad NFE exome
AF:
0.143
Gnomad OTH exome
AF:
0.124
GnomAD4 exome
AF:
0.133
AC:
193944
AN:
1461528
Hom.:
14180
AF XY:
0.132
AC XY:
95950
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.0206
Gnomad4 AMR exome
AF:
0.0646
Gnomad4 ASJ exome
AF:
0.134
Gnomad4 EAS exome
AF:
0.00313
Gnomad4 SAS exome
AF:
0.0775
Gnomad4 FIN exome
AF:
0.236
Gnomad4 NFE exome
AF:
0.143
Gnomad4 OTH exome
AF:
0.121
Alfa
AF:
0.130
Hom.:
2922
Bravo
AF:
0.0928
TwinsUK
AF:
0.140
AC:
518
ALSPAC
AF:
0.148
AC:
572
ESP6500AA
AF:
0.0284
AC:
125
ESP6500EA
AF:
0.140
AC:
1205
ExAC
AF:
0.110
AC:
13333
Asia WGS
AF:
0.0370
AC:
130
AN:
3476
EpiCase
AF:
0.141
EpiControl
AF:
0.139

ClinVar

Significance: Benign
Submissions summary: Benign:21Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:9Other:1
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
not provided, no classification providedreference populationITMISep 19, 2013- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, Part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant 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 -
Likely benign, no assertion criteria providedclinical testingGenetic Services Laboratory, University of Chicago-Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 21, 2015- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, no assertion criteria providedclinical testingClinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute-- -
Ataxia-telangiectasia syndrome Benign:4
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 01, 2021- -
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015This variant is associated with the following publications: (PMID: 25591549, 31382929, 28652578, 18502988, 24728327, 16914028, 27599564, 27153395, 17333338, 15756685, 22792358, 22529920, 20396981, 18465141, 17517479, 23585524, 24599715, 19147782, 17351744) -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesNov 28, 2022- -
Benign, criteria provided, single submitterclinical testingAthena Diagnostics IncJul 12, 2017- -
Hereditary cancer-predisposing syndrome Benign:3
Benign, criteria provided, single submitterclinical testingAmbry GeneticsJun 12, 2015This alteration is classified as benign based on a combination of the following: 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. -
Benign, criteria provided, single submittercurationSema4, Sema4May 03, 2021- -
Benign, criteria provided, single submitterclinical testingColor Diagnostics, LLC DBA Color HealthNov 05, 2014- -
Familial cancer of breast Benign:1
Benign, criteria provided, single submitterclinical testingKCCC/NGS Laboratory, Kuwait Cancer Control CenterJul 07, 2023- -
Hereditary breast ovarian cancer syndrome Benign:1
Benign, criteria provided, single submitterclinical testingNational Health Laboratory Service, Universitas Academic Hospital and University of the Free StateApr 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.37
Cadd
Benign
23
Dann
Uncertain
1.0
DEOGEN2
Benign
0.099
T;T
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.82
T;.
MetaRNN
Benign
0.0014
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
0.000051
P;P
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.12
Sift
Benign
0.20
T;T
Sift4G
Benign
0.13
T;T
Polyphen
0.044
B;B
Vest4
0.31
MPC
0.13
ClinPred
0.011
T
GERP RS
5.5
Varity_R
0.44
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs1801516; hg19: chr11-108175462; COSMIC: COSV53728020; COSMIC: COSV53728020; API