chr11-108229159-G-A

Variant names:

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

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

ATM links:

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=-0.77).

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
ATM	NM_000051.4 link	c.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
ATM	ENST00000675843.1 link	c.186-19G>A		intron_variant	Intron 3 of 62		NM_000051.4	ENSP00000501606.1		Q13315

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152106

Hom.:

Cov.:

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:

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:

AN:

1451554

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

721538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.00

AC:

AN:

43864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25916

East Asian (EAS)

AF:

0.00

AC:

AN:

39422

South Asian (SAS)

AF:

0.00

AC:

AN:

84816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.00000633

AC:

AN:

1105812

Other (OTH)

AF:

0.00

AC:

AN:

59934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

AN:

152106

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.0000655

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

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

(source)

DANN

Benign

0.72

PhyloP100

-0.16

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over