rs664677

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.3078-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,221,380 control chromosomes in the GnomAD database, including 216,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32574 hom., cov: 32)

Exomes 𝑓: 0.58 ( 184251 hom. )

Consequence

ATM
NM_000051.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.433

Publications

70 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=-0.9).

BP6

Variant 11-108272455-C-T is Benign according to our data. Variant chr11-108272455-C-T is described in ClinVar as Benign. ClinVar VariationId is 439418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 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.3078-77C>T		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3078-77C>T		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATM	ENST00000675843.1	MANE Select	c.3078-77C>T	intron	N/A	ENSP00000501606.1	Q13315
ATM	ENST00000452508.7	TSL:1	c.3078-77C>T	intron	N/A	ENSP00000388058.2	Q13315
ATM	ENST00000531525.3	TSL:1	c.3078-77C>T	intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes

AF:

0.647

AC:

98265

AN:

151956

Hom.:

32524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.673

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.653

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.577

Gnomad OTH

AF:

0.654

GnomAD4 exome

AF:

0.584

AC:

623986

AN:

1069306

Hom.:

184251

AF XY:

0.586

AC XY:

321831

AN XY:

548864

show subpopulations

African (AFR)

AF:

0.783

AC:

19881

AN:

25378

American (AMR)

AF:

0.656

AC:

27968

AN:

42626

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

15218

AN:

23496

East Asian (EAS)

AF:

0.403

AC:

15149

AN:

37598

South Asian (SAS)

AF:

0.646

AC:

49587

AN:

76806

European-Finnish (FIN)

AF:

0.627

AC:

33061

AN:

52704

Middle Eastern (MID)

AF:

0.757

AC:

3067

AN:

4054

European-Non Finnish (NFE)

AF:

0.568

AC:

431747

AN:

759522

Other (OTH)

AF:

0.601

AC:

28308

AN:

47122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

13324

26648

39973

53297

66621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10018

20036

30054

40072

50090

<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:

0.647

AC:

98366

AN:

152074

Hom.:

32574

Cov.:

AF XY:

0.650

AC XY:

48325

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.783

AC:

32473

AN:

41492

American (AMR)

AF:

0.672

AC:

10260

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.673

AC:

2337

AN:

3470

East Asian (EAS)

AF:

0.397

AC:

2043

AN:

5152

South Asian (SAS)

AF:

0.653

AC:

3152

AN:

4824

European-Finnish (FIN)

AF:

0.632

AC:

6670

AN:

10562

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.577

AC:

39244

AN:

67996

Other (OTH)

AF:

0.654

AC:

1378

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1704

3408

5112

6816

8520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.586

Hom.:

8428

Bravo

AF:

0.653

Asia WGS

AF:

0.590

AC:

2049

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Ataxia-telangiectasia syndrome (2)

not provided (2)

Hereditary breast ovarian cancer syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.26

PhyloP100

-0.43

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