rs609261

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000051.4(ATM):c.3994-193T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 386,940 control chromosomes in the GnomAD database, including 58,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21764 hom., cov: 31)

Exomes 𝑓: 0.55 ( 37020 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.481

Publications

46 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-108287407-T-C is Benign according to our data. Variant chr11-108287407-T-C is described in ClinVar as Benign. ClinVar VariationId is 516633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.631 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.3994-193T>C		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3994-193T>C		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3994-193T>C	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3994-193T>C	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3994-193T>C	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79760

AN:

151846

Hom.:

21754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.559

GnomAD4 exome

AF:

0.552

AC:

129709

AN:

234976

Hom.:

37020

Cov.:

AF XY:

0.557

AC XY:

68660

AN XY:

123172

show subpopulations

African (AFR)

AF:

0.381

AC:

2492

AN:

6546

American (AMR)

AF:

0.610

AC:

5348

AN:

8762

Ashkenazi Jewish (ASJ)

AF:

0.607

AC:

4855

AN:

8002

East Asian (EAS)

AF:

0.397

AC:

7594

AN:

19108

South Asian (SAS)

AF:

0.618

AC:

6773

AN:

10952

European-Finnish (FIN)

AF:

0.618

AC:

7873

AN:

12736

Middle Eastern (MID)

AF:

0.725

AC:

771

AN:

1064

European-Non Finnish (NFE)

AF:

0.562

AC:

86025

AN:

153104

Other (OTH)

AF:

0.543

AC:

7978

AN:

14702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2673

5346

8020

10693

13366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.525

AC:

79794

AN:

151964

Hom.:

21764

Cov.:

AF XY:

0.533

AC XY:

39611

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.382

AC:

15837

AN:

41460

American (AMR)

AF:

0.615

AC:

9383

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.641

AC:

2224

AN:

3468

East Asian (EAS)

AF:

0.385

AC:

1992

AN:

5168

South Asian (SAS)

AF:

0.650

AC:

3129

AN:

4816

European-Finnish (FIN)

AF:

0.630

AC:

6619

AN:

10512

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.568

AC:

38612

AN:

67958

Other (OTH)

AF:

0.560

AC:

1181

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1847

3694

5541

7388

9235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.556

Hom.:

72218

Bravo

AF:

0.514

Asia WGS

AF:

0.550

AC:

1913

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ataxia-telangiectasia syndrome (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.5

(source)

DANN

Benign

0.37

PhyloP100

-0.48

PromoterAI

-0.0047

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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