chr11-108229159-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000051.4(ATM):​c.186-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000499 in 1,603,660 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.156

Publications

1 publications found
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 Gene-Disease associations (from GenCC):
  • hereditary breast carcinoma
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
  • ataxia telangiectasia
    Inheritance: 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 cancer
    Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
  • prostate cancer
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • sarcoma
    Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
  • familial ovarian cancer
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • gastric carcinoma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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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=-0.77).
BP6
Variant 11-108229159-G-A is Benign according to our data. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108229159-G-A is described in CliVar as Likely_benign. Clinvar id is 385043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATMNM_000051.4 linkc.186-19G>A intron_variant Intron 3 of 62 ENST00000675843.1 NP_000042.3 Q13315A0A024R3C7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATMENST00000675843.1 linkc.186-19G>A intron_variant Intron 3 of 62 NM_000051.4 ENSP00000501606.1 Q13315

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152106
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000126
AC:
3
AN:
238738
AF XY:
0.0000154
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000282
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000482
AC:
7
AN:
1451554
Hom.:
0
Cov.:
31
AF XY:
0.00000416
AC XY:
3
AN XY:
721538
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33134
American (AMR)
AF:
0.00
AC:
0
AN:
43864
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25916
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39422
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53056
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5600
European-Non Finnish (NFE)
AF:
0.00000633
AC:
7
AN:
1105812
Other (OTH)
AF:
0.00
AC:
0
AN:
59934
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152106
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74300
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41412
American (AMR)
AF:
0.0000655
AC:
1
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5200
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 21, 2016
GeneDx
Significance:Likely 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:1
Nov 26, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Familial cancer of breast Benign:1
Apr 17, 2024
Myriad Genetics, Inc.
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Hereditary cancer-predisposing syndrome Benign:1
Aug 30, 2017
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
12
DANN
Benign
0.72
PhyloP100
-0.16
Mutation Taster
=89/11
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs748791429; hg19: chr11-108099886; API