rs1555091083

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000051.4(ATM):c.3403-15delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,467,312 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point.. The gene ATM is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.301

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):

ATM-related cancer predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
ataxia telangiectasia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Laboratory for Molecular Medicine
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
gastric carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATM links:

Genome browser will be placed here

ACMG classification

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP6

Variant 11-108280970-AT-A is Benign according to our data. Variant chr11-108280970-AT-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2692170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.3403-15delT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3403-15delT		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3403-24delT	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3403-24delT	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3403-24delT	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.000181

AC:

AN:

105084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000229

Gnomad SAS

AF:

0.00109

Gnomad FIN

AF:

0.000159

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000195

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000820

AC:

128

AN:

156048

AF XY:

0.000957

show subpopulations

Gnomad AFR exome

AF:

0.000335

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.00101

Gnomad EAS exome

AF:

0.000961

Gnomad FIN exome

AF:

0.000596

Gnomad NFE exome

AF:

0.000600

Gnomad OTH exome

AF:

0.000277

GnomAD4 exome

AF:

0.000530

AC:

722

AN:

1362130

Hom.:

Cov.:

AF XY:

0.000539

AC XY:

367

AN XY:

680648

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000359

AC:

AN:

30618

American (AMR)

AF:

0.000312

AC:

AN:

41708

Ashkenazi Jewish (ASJ)

AF:

0.000404

AC:

AN:

24744

East Asian (EAS)

AF:

0.000505

AC:

AN:

37610

South Asian (SAS)

AF:

0.00113

AC:

AN:

81086

European-Finnish (FIN)

AF:

0.000258

AC:

AN:

50340

Middle Eastern (MID)

AF:

0.000182

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.000515

AC:

533

AN:

1033954

Other (OTH)

AF:

0.000530

AC:

AN:

56570

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.345

Heterozygous variant carriers

154

230

307

384

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.000190

AC:

AN:

105182

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

50720

show subpopulations

African (AFR)

AF:

0.000184

AC:

AN:

32552

American (AMR)

AF:

0.00

AC:

AN:

9110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2060

East Asian (EAS)

AF:

0.000229

AC:

AN:

4366

South Asian (SAS)

AF:

0.00109

AC:

AN:

2742

European-Finnish (FIN)

AF:

0.000159

AC:

AN:

6276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.000195

AC:

AN:

46056

Other (OTH)

AF:

0.00

AC:

AN:

1360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000210

Hom.:

Bravo

AF:

0.000144

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial cancer of breast (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over