rs112018640
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001184.4(ATR):c.5868C>T(p.Tyr1956=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00964 in 1,549,054 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.011 ( 21 hom., cov: 28)
Exomes 𝑓: 0.0096 ( 268 hom. )
Consequence
ATR
NM_001184.4 synonymous
NM_001184.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.817
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 3-142496391-G-A is Benign according to our data. Variant chr3-142496391-G-A is described in ClinVar as [Benign]. Clinvar id is 157996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142496391-G-A is described in Lovd as [Likely_benign]. Variant chr3-142496391-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.817 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0105 (1433/136252) while in subpopulation SAS AF= 0.0246 (102/4140). AF 95% confidence interval is 0.0208. There are 21 homozygotes in gnomad4. There are 665 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 21 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATR | NM_001184.4 | c.5868C>T | p.Tyr1956= | synonymous_variant | 34/47 | ENST00000350721.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATR | ENST00000350721.9 | c.5868C>T | p.Tyr1956= | synonymous_variant | 34/47 | 1 | NM_001184.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0105 AC: 1433AN: 136164Hom.: 21 Cov.: 28
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GnomAD3 exomes AF: 0.00920 AC: 2268AN: 246470Hom.: 77 AF XY: 0.0102 AC XY: 1358AN XY: 133100
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GnomAD4 exome AF: 0.00956 AC: 13505AN: 1412802Hom.: 268 Cov.: 31 AF XY: 0.0101 AC XY: 7105AN XY: 702812
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GnomAD4 genome ? AF: 0.0105 AC: 1433AN: 136252Hom.: 21 Cov.: 28 AF XY: 0.0102 AC XY: 665AN XY: 65312
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ClinVar
Significance: Benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 05, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 02, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Seckel syndrome 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at