chr11-108225326-A-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000051.4(ATM):c.-31+2140A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,366 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.030 ( 109 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATM
NM_000051.4 intron
NM_000051.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.325
Publications
6 publications found
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 Gene-Disease associations (from GenCC):
- hereditary breast carcinomaInheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
- ataxia telangiectasiaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Orphanet
- hereditary nonpolyposis colon cancerInheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
- prostate cancerInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- sarcomaInheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
- familial ovarian cancerInheritance: AD Classification: LIMITED Submitted by: ClinGen
- gastric carcinomaInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0301 (4579/152366) while in subpopulation NFE AF = 0.045 (3063/68028). AF 95% confidence interval is 0.0437. There are 109 homozygotes in GnomAd4. There are 2163 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 109 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATM | NM_000051.4 | c.-31+2140A>T | intron_variant | Intron 1 of 62 | ENST00000675843.1 | NP_000042.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0301 AC: 4579AN: 152248Hom.: 109 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
4579
AN:
152248
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 6Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 4
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
6
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
4
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
AC:
0
AN:
4
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
AC:
0
AN:
2
Other (OTH)
AC:
0
AN:
0
GnomAD4 genome AF: 0.0301 AC: 4579AN: 152366Hom.: 109 Cov.: 33 AF XY: 0.0290 AC XY: 2163AN XY: 74514 show subpopulations
GnomAD4 genome
AF:
AC:
4579
AN:
152366
Hom.:
Cov.:
33
AF XY:
AC XY:
2163
AN XY:
74514
show subpopulations
African (AFR)
AF:
AC:
330
AN:
41594
American (AMR)
AF:
AC:
305
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
AC:
168
AN:
3470
East Asian (EAS)
AF:
AC:
3
AN:
5190
South Asian (SAS)
AF:
AC:
119
AN:
4830
European-Finnish (FIN)
AF:
AC:
417
AN:
10626
Middle Eastern (MID)
AF:
AC:
5
AN:
294
European-Non Finnish (NFE)
AF:
AC:
3063
AN:
68028
Other (OTH)
AF:
AC:
61
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
237
473
710
946
1183
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
54
108
162
216
270
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
51
AN:
3478
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.