1-11013784-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_007375.4(TARDBP):āc.57A>Gā(p.Pro19=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000059 ( 0 hom., cov: 33)
Exomes š: 0.000017 ( 0 hom. )
Consequence
TARDBP
NM_007375.4 synonymous
NM_007375.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.33
Genes affected
TARDBP (HGNC:11571): (TAR DNA binding protein) HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 1-11013784-A-G is Benign according to our data. Variant chr1-11013784-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 875642.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-3.33 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000591 (9/152372) while in subpopulation EAS AF= 0.00115 (6/5196). AF 95% confidence interval is 0.000502. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 9 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TARDBP | NM_007375.4 | c.57A>G | p.Pro19= | synonymous_variant | 2/6 | ENST00000240185.8 | NP_031401.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TARDBP | ENST00000240185.8 | c.57A>G | p.Pro19= | synonymous_variant | 2/6 | 1 | NM_007375.4 | ENSP00000240185 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152254Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000519 AC: 13AN: 250492Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135434
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461426Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727014
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152372Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74524
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Amyotrophic lateral sclerosis type 10 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 15, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Amyotrophic lateral sclerosis type 10;C3150169:TARDBP-related frontotemporal dementia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 23, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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