Variant rs11927681 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001184.4(ATR):c.5380+121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 841,482 control chromosomes in the GnomAD database, including 3,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.070 ( 539 hom., cov: 32)

Exomes 𝑓: 0.085 ( 3048 hom. )

Consequence

ATR
NM_001184.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0940

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 3-142499506-G-T is Benign according to our data. Variant chr3-142499506-G-T is described in ClinVar as [Benign]. Clinvar id is 678211.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATR	NM_001184.4 link	c.5380+121C>A		intron_variant	Intron 31 of 46	ENST00000350721.9	NP_001175.2	Q13535-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATR	ENST00000350721.9 link	c.5380+121C>A		intron_variant	Intron 31 of 46	1	NM_001184.4	ENSP00000343741.4		Q13535-1

Frequencies

GnomAD3 genomes

AF:

0.0698

AC:

10603

AN:

151994

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.0697

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0206

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0964

GnomAD4 exome

AF:

0.0848

AC:

58444

AN:

689370

Hom.:

3048

AF XY:

0.0839

AC XY:

30997

AN XY:

369478

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

Gnomad4 AMR exome

AF:

0.0562

Gnomad4 ASJ exome

AF:

0.113

Gnomad4 EAS exome

AF:

0.000296

Gnomad4 SAS exome

AF:

0.0270

Gnomad4 FIN exome

AF:

0.0509

Gnomad4 NFE exome

AF:

0.108

Gnomad4 OTH exome

AF:

0.0835

GnomAD4 genome

AF:

0.0697

AC:

10601

AN:

152112

Hom.:

539

Cov.:

AF XY:

0.0665

AC XY:

4945

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.0697

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.0450

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.0950

Alfa

AF:

0.0830

Hom.:

Bravo

AF:

0.0721

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.95

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