rs11927681

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

2

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]

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/exons MANE UniProt
ATRNM_001184.4 linkuse as main transcriptc.5380+121C>A intron_variant ENST00000350721.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATRENST00000350721.9 linkuse as main transcriptc.5380+121C>A intron_variant 1 NM_001184.4 P1Q13535-1

Frequencies

GnomAD3 genomes
AF:
0.0698
AC:
10603
AN:
151994
Hom.:
539
Cov.:
32
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.:
32
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.:
88
Bravo
AF:
0.0721
Asia WGS
AF:
0.0140
AC:
48
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 submitterclinical testingGeneDxJun 16, 2018This 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
11
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.

Other links and lift over

dbSNP: rs11927681; hg19: chr3-142218348; API