rs2234996

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_StrongBS1BS2

The NM_000051.4(ATM):c.332-71A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 1,330,594 control chromosomes in the GnomAD database, including 1,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 64 hom., cov: 32)

Exomes 𝑓: 0.037 ( 1027 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.21

Publications

9 publications found

Variant links:

COSMIC-nc: COSV104591951

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=-0.87).

BP6

Variant 11-108235599-A-G is Benign according to our data. Variant chr11-108235599-A-G is described in ClinVar as Benign. ClinVar VariationId is 1179574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0257 (3920/152360) while in subpopulation SAS AF = 0.0476 (230/4834). AF 95% confidence interval is 0.0425. There are 64 homozygotes in GnomAd4. There are 1835 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AD,AR gene

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.332-71A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.332-71A>G		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.332-71A>G	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.332-71A>G	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.332-71A>G	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3924

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00776

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0795

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0477

Gnomad FIN

AF:

0.00791

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0378

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.0371

AC:

43661

AN:

1178234

Hom.:

1027

AF XY:

0.0372

AC XY:

22030

AN XY:

592146

show subpopulations

African (AFR)

AF:

0.00667

AC:

175

AN:

26246

American (AMR)

AF:

0.0190

AC:

661

AN:

34762

Ashkenazi Jewish (ASJ)

AF:

0.0834

AC:

1991

AN:

23880

East Asian (EAS)

AF:

0.000142

AC:

AN:

35122

South Asian (SAS)

AF:

0.0455

AC:

3392

AN:

74474

European-Finnish (FIN)

AF:

0.0110

AC:

493

AN:

44706

Middle Eastern (MID)

AF:

0.0273

AC:

100

AN:

3658

European-Non Finnish (NFE)

AF:

0.0397

AC:

35105

AN:

884990

Other (OTH)

AF:

0.0345

AC:

1739

AN:

50396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

2070

4140

6210

8280

10350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1258

2516

3774

5032

6290

<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:

0.0257

AC:

3920

AN:

152360

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1835

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00774

AC:

322

AN:

41594

American (AMR)

AF:

0.0212

AC:

324

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0795

AC:

276

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.0476

AC:

230

AN:

4834

European-Finnish (FIN)

AF:

0.00791

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0378

AC:

2574

AN:

68024

Other (OTH)

AF:

0.0312

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

203

406

608

811

1014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0305

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.0210

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.5

(source)

DANN

Benign

0.82

PhyloP100

-1.2

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