chr3-142449489-C-T

Position:

chr3-142449489-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001184.4(ATR):c.7875G>A(p.Gln2625=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,613,102 control chromosomes in the GnomAD database, including 612,694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60127 hom., cov: 32)

Exomes 𝑓: 0.87 ( 552567 hom. )

Consequence

ATR
NM_001184.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.24

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-142449489-C-T is Benign according to our data. Variant chr3-142449489-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 93669.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142449489-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ATR	NM_001184.4 linkuse as main transcript	c.7875G>A	p.Gln2625=	synonymous_variant	47/47	ENST00000350721.9	NP_001175.2
ATR	NM_001354579.2 linkuse as main transcript	c.7683G>A	p.Gln2561=	synonymous_variant	46/46		NP_001341508.1
ATR	XM_011512924.2 linkuse as main transcript	c.7881G>A	p.Gln2627=	synonymous_variant	47/47		XP_011511226.1
ATR	XM_011512925.2 linkuse as main transcript	c.7689G>A	p.Gln2563=	synonymous_variant	46/46		XP_011511227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9 linkuse as main transcript	c.7875G>A	p.Gln2625=	synonymous_variant	47/47	1	NM_001184.4	ENSP00000343741	P1	Q13535-1

Frequencies

GnomAD3 genomes

AF:

0.887

AC:

134880

AN:

152128

Hom.:

60074

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

0.839

Gnomad AMR

AF:

0.807

Gnomad ASJ

AF:

0.784

Gnomad EAS

AF:

0.929

Gnomad SAS

AF:

0.938

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.866

Gnomad OTH

AF:

0.872

GnomAD3 exomes

AF:

0.858

AC:

215739

AN:

251404

Hom.:

93115

AF XY:

0.863

AC XY:

117273

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.973

Gnomad AMR exome

AF:

0.756

Gnomad ASJ exome

AF:

0.777

Gnomad EAS exome

AF:

0.933

Gnomad SAS exome

AF:

0.937

Gnomad FIN exome

AF:

0.811

Gnomad NFE exome

AF:

0.856

Gnomad OTH exome

AF:

0.843

GnomAD4 exome

AF:

0.869

AC:

1269266

AN:

1460856

Hom.:

552567

Cov.:

AF XY:

0.871

AC XY:

632790

AN XY:

726804

show subpopulations

Gnomad4 AFR exome

AF:

0.974

Gnomad4 AMR exome

AF:

0.765

Gnomad4 ASJ exome

AF:

0.775

Gnomad4 EAS exome

AF:

0.908

Gnomad4 SAS exome

AF:

0.935

Gnomad4 FIN exome

AF:

0.810

Gnomad4 NFE exome

AF:

0.868

Gnomad4 OTH exome

AF:

0.876

GnomAD4 genome

AF:

0.887

AC:

134988

AN:

152246

Hom.:

60127

Cov.:

AF XY:

0.883

AC XY:

65740

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.970

Gnomad4 AMR

AF:

0.806

Gnomad4 ASJ

AF:

0.784

Gnomad4 EAS

AF:

0.929

Gnomad4 SAS

AF:

0.939

Gnomad4 FIN

AF:

0.804

Gnomad4 NFE

AF:

0.866

Gnomad4 OTH

AF:

0.874

Alfa

AF:

0.865

Hom.:

92734

Bravo

AF:

0.887

Asia WGS

AF:

0.937

AC:

3256

AN:

3478

EpiCase

AF:

0.863

EpiControl

AF:

0.858

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 25, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 26, 2016	Variant summary: The c.7875G>A variant affects a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts polymorphism outcome for this variant. 3/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts changes of binding motifs for splicing enhancers. However, these predictions are not confirmed by experimental studies. This variant is found in 104951/121386 control chromosomes (45665 homozygotes) at a frequency of 0.8646055, which is about 1383368 times of the maximal expected frequency of a pathogenic allele (0.0000006) in this gene. Taking together, based on the prevalence of this variant in general population the variant was classified as Benign. -

Seckel syndrome 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

3.3

DANN

Benign

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over