rs142240637
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001184.4(ATR):c.4764C>T(p.Leu1588=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000726 in 1,613,930 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0038 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 0 hom. )
Consequence
ATR
NM_001184.4 synonymous
NM_001184.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.365
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 3-142512348-G-A is Benign according to our data. Variant chr3-142512348-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-142512348-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00382 (581/152120) while in subpopulation AFR AF= 0.0137 (567/41478). AF 95% confidence interval is 0.0127. There are 11 homozygotes in gnomad4. There are 257 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 11 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATR | NM_001184.4 | c.4764C>T | p.Leu1588= | synonymous_variant | 27/47 | ENST00000350721.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATR | ENST00000350721.9 | c.4764C>T | p.Leu1588= | synonymous_variant | 27/47 | 1 | NM_001184.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00381 AC: 579AN: 152002Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00102 AC: 257AN: 251456Hom.: 5 AF XY: 0.000648 AC XY: 88AN XY: 135902
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GnomAD4 exome AF: 0.000404 AC: 590AN: 1461810Hom.: 0 Cov.: 35 AF XY: 0.000320 AC XY: 233AN XY: 727218
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GnomAD4 genome ? AF: 0.00382 AC: 581AN: 152120Hom.: 11 Cov.: 32 AF XY: 0.00346 AC XY: 257AN XY: 74384
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | ATR: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
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. - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 29, 2021 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at