11-108280970-AT-ATT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000051.4(ATM):c.3403-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,467,080 control chromosomes in the GnomAD database, including 934 homozygotes. Variant has been reported in ClinVar as 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 0.073 ( 640 hom., cov: 31)

Exomes 𝑓: 0.0064 ( 294 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.301

Publications

0 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 -16 ACMG points.

BP6

Variant 11-108280970-A-AT is Benign according to our data. Variant chr11-108280970-A-AT is described in ClinVar as Benign. ClinVar VariationId is 235644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

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.3403-15dupT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3403-15dupT		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3403-25_3403-24insT	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3403-25_3403-24insT	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3403-25_3403-24insT	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0724

AC:

7606

AN:

105064

Hom.:

631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.00191

Gnomad AMR

AF:

0.0465

Gnomad ASJ

AF:

0.00631

Gnomad EAS

AF:

0.00114

Gnomad SAS

AF:

0.00218

Gnomad FIN

AF:

0.000319

Gnomad MID

AF:

0.0208

Gnomad NFE

AF:

0.00191

Gnomad OTH

AF:

0.0697

GnomAD2 exomes

AF:

0.0206

AC:

3217

AN:

156048

AF XY:

0.0162

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0235

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.000852

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.00645

AC:

8781

AN:

1361918

Hom.:

294

Cov.:

AF XY:

0.00566

AC XY:

3855

AN XY:

680542

show subpopulations

African (AFR)

AF:

0.168

AC:

5139

AN:

30570

American (AMR)

AF:

0.0152

AC:

636

AN:

41736

Ashkenazi Jewish (ASJ)

AF:

0.00493

AC:

122

AN:

24738

East Asian (EAS)

AF:

0.000532

AC:

AN:

37620

South Asian (SAS)

AF:

0.000950

AC:

AN:

81078

European-Finnish (FIN)

AF:

0.000675

AC:

AN:

50352

Middle Eastern (MID)

AF:

0.0189

AC:

104

AN:

5504

European-Non Finnish (NFE)

AF:

0.00170

AC:

1758

AN:

1033750

Other (OTH)

AF:

0.0158

AC:

891

AN:

56570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

331

662

994

1325

1656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

202

404

606

808

1010

<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:

0.0727

AC:

7646

AN:

105162

Hom.:

640

Cov.:

AF XY:

0.0711

AC XY:

3607

AN XY:

50712

show subpopulations

African (AFR)

AF:

0.216

AC:

7013

AN:

32536

American (AMR)

AF:

0.0463

AC:

422

AN:

9106

Ashkenazi Jewish (ASJ)

AF:

0.00631

AC:

AN:

2060

East Asian (EAS)

AF:

0.00115

AC:

AN:

4366

South Asian (SAS)

AF:

0.00182

AC:

AN:

2742

European-Finnish (FIN)

AF:

0.000319

AC:

AN:

6276

Middle Eastern (MID)

AF:

0.0221

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.00191

AC:

AN:

46056

Other (OTH)

AF:

0.0691

AC:

AN:

1360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

303

606

909

1212

1515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.00141

Hom.:

Bravo

AF:

0.0582

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Ataxia-telangiectasia syndrome (1)

Breast and/or ovarian cancer (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.30

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism (auto)

(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