dbSNP rs13091637: ATR:c.3357+128G>A (chr3-142547597-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001184.4(ATR):c.3357+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,061,372 control chromosomes in the GnomAD database, including 20,026 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2314 hom., cov: 32)

Exomes 𝑓: 0.19 ( 17712 hom. )

Consequence

ATR
NM_001184.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

Publications

10 publications found

Variant links:

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-142547597-C-T is Benign according to our data. Variant chr3-142547597-C-T is described in ClinVar as Benign. ClinVar VariationId is 1266052.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATR	NM_001184.4 link	c.3357+128G>A		intron_variant	Intron 16 of 46	ENST00000350721.9	NP_001175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9 link	c.3357+128G>A		intron_variant	Intron 16 of 46	1	NM_001184.4	ENSP00000343741.4

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25006

AN:

151846

Hom.:

2318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.169

GnomAD4 exome

AF:

0.192

AC:

174642

AN:

909410

Hom.:

17712

AF XY:

0.190

AC XY:

88023

AN XY:

462974

show subpopulations

African (AFR)

AF:

0.0616

AC:

1269

AN:

20594

American (AMR)

AF:

0.201

AC:

4979

AN:

24724

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

4864

AN:

20070

East Asian (EAS)

AF:

0.165

AC:

5481

AN:

33288

South Asian (SAS)

AF:

0.122

AC:

7532

AN:

61602

European-Finnish (FIN)

AF:

0.225

AC:

7781

AN:

34598

Middle Eastern (MID)

AF:

0.164

AC:

600

AN:

3656

European-Non Finnish (NFE)

AF:

0.200

AC:

134089

AN:

669234

Other (OTH)

AF:

0.193

AC:

8047

AN:

41644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

6762

13524

20287

27049

33811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3822

7644

11466

15288

19110

<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:

0.165

AC:

25001

AN:

151962

Hom.:

2314

Cov.:

AF XY:

0.167

AC XY:

12381

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.0700

AC:

2899

AN:

41438

American (AMR)

AF:

0.207

AC:

3155

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

827

AN:

3464

East Asian (EAS)

AF:

0.154

AC:

799

AN:

5186

South Asian (SAS)

AF:

0.132

AC:

636

AN:

4820

European-Finnish (FIN)

AF:

0.226

AC:

2383

AN:

10522

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13799

AN:

67948

Other (OTH)

AF:

0.167

AC:

352

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1070

2141

3211

4282

5352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.189

Hom.:

1452

Bravo

AF:

0.161

Asia WGS

AF:

0.132

AC:

457

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

(source)

DANN

Benign

0.84

PhyloP100

-1.3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over