rs201106004

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001184.4(ATR):c.7041+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,493,560 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

ATR
NM_001184.4 splice_region, intron

Scores

Splicing: ADA: 0.006630

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:4

Conservation

PhyloP100: 0.0940

Publications

2 publications found

Variant links:

COSMIC-nc: COSV104670838

Genes affected

ATR (HGNC:882): (ATR serine/threonine kinase) The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ATR Gene-Disease associations (from GenCC):

Seckel syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Illumina
familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome
Inheritance: AD, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
sarcoma
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
Seckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial prostate carcinoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ATR links:

ENSG00000295506 (HGNC:):

ENSG00000295506 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 3-142465089-C-T is Benign according to our data. Variant chr3-142465089-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434449.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184.4. 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
	ATR	NM_001184.4	MANE Select	c.7041+8G>A		splice_region intron	N/A	NP_001175.2	Q13535-1
	ATR	NM_001354579.2		c.6849+8G>A		splice_region intron	N/A	NP_001341508.1	Q13535-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATR	ENST00000350721.9	TSL:1 MANE Select	c.7041+8G>A	splice_region intron	N/A	ENSP00000343741.4	Q13535-1
ATR	ENST00000513291.2	TSL:1	n.2225+8G>A	splice_region intron	N/A
ATR	ENST00000936442.1		c.6888+8G>A	splice_region intron	N/A	ENSP00000606501.1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

154

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000671

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00175

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00109

AC:

227

AN:

208780

AF XY:

0.000946

show subpopulations

Gnomad AFR exome

AF:

0.000302

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00165

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000717

Gnomad NFE exome

AF:

0.00192

Gnomad OTH exome

AF:

0.000633

GnomAD4 exome

AF:

0.00126

AC:

1695

AN:

1341618

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

828

AN XY:

663496

show subpopulations

African (AFR)

AF:

0.000168

AC:

AN:

29694

American (AMR)

AF:

0.0000292

AC:

AN:

34280

Ashkenazi Jewish (ASJ)

AF:

0.00156

AC:

AN:

23084

East Asian (EAS)

AF:

0.00

AC:

AN:

36276

South Asian (SAS)

AF:

0.000199

AC:

AN:

60268

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

48438

Middle Eastern (MID)

AF:

0.000417

AC:

AN:

4798

European-Non Finnish (NFE)

AF:

0.00145

AC:

1522

AN:

1050022

Other (OTH)

AF:

0.00117

AC:

AN:

54758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

145

217

290

362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.00101

AC:

154

AN:

151942

Hom.:

Cov.:

AF XY:

0.000996

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41534

American (AMR)

AF:

0.000393

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000671

AC:

AN:

10436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00175

AC:

119

AN:

67930

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00133

Hom.:

Bravo

AF:

0.000816

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ATR-related disorder (1)

not specified (1)

Seckel syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.4

(source)

DANN

Benign

0.65

PhyloP100

0.094

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0066

dbscSNV1_RF

Benign

0.67

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