rs10804682

Variant summary

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

The NM_001184.4(ATR):​c.4383-177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,976 control chromosomes in the GnomAD database, including 2,008 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.15 ( 2008 hom., cov: 31)

Consequence

ATR
NM_001184.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.664
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=-0.85).
BP6
Variant 3-142515692-G-A is Benign according to our data. Variant chr3-142515692-G-A is described in ClinVar as [Benign]. Clinvar id is 678203.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATRNM_001184.4 linkuse as main transcriptc.4383-177C>T intron_variant ENST00000350721.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATRENST00000350721.9 linkuse as main transcriptc.4383-177C>T intron_variant 1 NM_001184.4 P1Q13535-1
ATRENST00000661310.1 linkuse as main transcriptc.4191-177C>T intron_variant Q13535-2
ATRENST00000656590.1 linkuse as main transcriptc.3173-177C>T intron_variant, NMD_transcript_variant
ATRENST00000653868.1 linkuse as main transcriptn.4412-177C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.147
AC:
22343
AN:
151858
Hom.:
2012
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0492
Gnomad AMI
AF:
0.466
Gnomad AMR
AF:
0.135
Gnomad ASJ
AF:
0.211
Gnomad EAS
AF:
0.0784
Gnomad SAS
AF:
0.108
Gnomad FIN
AF:
0.156
Gnomad MID
AF:
0.263
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.176
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.147
AC:
22342
AN:
151976
Hom.:
2008
Cov.:
31
AF XY:
0.145
AC XY:
10740
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0493
Gnomad4 AMR
AF:
0.134
Gnomad4 ASJ
AF:
0.211
Gnomad4 EAS
AF:
0.0783
Gnomad4 SAS
AF:
0.108
Gnomad4 FIN
AF:
0.156
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.174
Alfa
AF:
0.193
Hom.:
3999
Bravo
AF:
0.141
Asia WGS
AF:
0.105
AC:
362
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
-0.85
CADD
Benign
6.0
DANN
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs10804682; hg19: chr3-142234534; API