11-108279480-CT-C

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.3285-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,573,082 control chromosomes in the GnomAD database, including 14,912 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1202 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13710 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:20

Conservation

PhyloP100: 0.508

Publications

19 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

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 11-108279480-CT-C is Benign according to our data. Variant chr11-108279480-CT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 181857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 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.3285-9delT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3285-9delT		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3285-10delT	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3285-10delT	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3285-10delT	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16172

AN:

152030

Hom.:

1202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0239

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.0918

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.00788

Gnomad SAS

AF:

0.0753

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.145

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.113

AC:

25710

AN:

227570

AF XY:

0.115

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.0614

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.00632

Gnomad FIN exome

AF:

0.241

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.132

AC:

187000

AN:

1420934

Hom.:

13710

Cov.:

AF XY:

0.131

AC XY:

92695

AN XY:

707534

show subpopulations

African (AFR)

AF:

0.0209

AC:

682

AN:

32554

American (AMR)

AF:

0.0646

AC:

2745

AN:

42482

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

3437

AN:

25698

East Asian (EAS)

AF:

0.00314

AC:

123

AN:

39140

South Asian (SAS)

AF:

0.0772

AC:

6505

AN:

84220

European-Finnish (FIN)

AF:

0.235

AC:

12359

AN:

52672

Middle Eastern (MID)

AF:

0.119

AC:

677

AN:

5696

European-Non Finnish (NFE)

AF:

0.142

AC:

153389

AN:

1079588

Other (OTH)

AF:

0.120

AC:

7083

AN:

58884

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7299

14598

21898

29197

36496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5266

10532

15798

21064

26330

<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:

0.106

AC:

16175

AN:

152148

Hom.:

1202

Cov.:

AF XY:

0.108

AC XY:

8065

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0239

AC:

995

AN:

41560

American (AMR)

AF:

0.0916

AC:

1400

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3470

East Asian (EAS)

AF:

0.00790

AC:

AN:

5188

South Asian (SAS)

AF:

0.0762

AC:

367

AN:

4816

European-Finnish (FIN)

AF:

0.237

AC:

2512

AN:

10578

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.145

AC:

9821

AN:

67950

Other (OTH)

AF:

0.103

AC:

217

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

705

1410

2114

2819

3524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.125

Hom.:

256

Bravo

AF:

0.0928

Asia WGS

AF:

0.0370

AC:

128

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

Ataxia-telangiectasia syndrome (4)

not provided (3)

Hereditary cancer-predisposing syndrome (2)

Familial cancer of breast (1)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.51

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