chr3-48467117-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_033629.6(TREX1):āc.462T>Cā(p.Asp154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,613,886 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0057 ( 6 hom., cov: 33)
Exomes š: 0.00055 ( 10 hom. )
Consequence
TREX1
NM_033629.6 synonymous
NM_033629.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00900
Genes affected
TREX1 (HGNC:12269): (three prime repair exonuclease 1) This gene encodes a nuclear protein with 3' exonuclease activity. The encoded protein may play a role in DNA repair and serve as a proofreading function for DNA polymerase. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, Cree encephalitis, and other diseases of the immune system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2012]
ATRIP (HGNC:33499): (ATR interacting protein) This gene encodes an essential component of the DNA damage checkpoint. The encoded protein binds to single-stranded DNA coated with replication protein A. The protein also interacts with the ataxia telangiectasia and Rad3 related protein kinase, resulting in its accumulation at intranuclear foci induced by DNA damage. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 3-48467117-T-C is Benign according to our data. Variant chr3-48467117-T-C is described in ClinVar as [Benign]. Clinvar id is 345778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48467117-T-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.009 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00568 (865/152214) while in subpopulation AFR AF= 0.0199 (828/41530). AF 95% confidence interval is 0.0188. There are 6 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 6 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREX1 | NM_033629.6 | c.462T>C | p.Asp154= | synonymous_variant | 2/2 | ENST00000625293.3 | |
ATRIP | NM_130384.3 | c.*1563T>C | 3_prime_UTR_variant | 13/13 | ENST00000320211.10 | ||
ATRIP-TREX1 | NR_153405.1 | n.3771T>C | non_coding_transcript_exon_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREX1 | ENST00000625293.3 | c.462T>C | p.Asp154= | synonymous_variant | 2/2 | NM_033629.6 | P1 | ||
ATRIP | ENST00000320211.10 | c.*1563T>C | 3_prime_UTR_variant | 13/13 | 1 | NM_130384.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00568 AC: 864AN: 152096Hom.: 6 Cov.: 33
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GnomAD3 exomes AF: 0.00156 AC: 391AN: 250650Hom.: 8 AF XY: 0.00119 AC XY: 161AN XY: 135534
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GnomAD4 exome AF: 0.000551 AC: 806AN: 1461672Hom.: 10 Cov.: 31 AF XY: 0.000474 AC XY: 345AN XY: 727140
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GnomAD4 genome AF: 0.00568 AC: 865AN: 152214Hom.: 6 Cov.: 33 AF XY: 0.00540 AC XY: 402AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1
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. - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Chilblain lupus 1;C0796126:Aicardi-Goutieres syndrome 1;C1860518:Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Aicardi-Goutieres syndrome 1 Benign:1
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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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