chr5-150361128-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001371623.1(TCOF1):c.109-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,614,056 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
TCOF1
NM_001371623.1 intron
NM_001371623.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.301
Genes affected
TCOF1 (HGNC:11654): (treacle ribosome biogenesis factor 1) This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 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=-0.81).
BP6
Variant 5-150361128-T-C is Benign according to our data. Variant chr5-150361128-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 209024.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00156 (237/152280) while in subpopulation AFR AF= 0.00544 (226/41560). AF 95% confidence interval is 0.00486. There are 0 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 237 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCOF1 | NM_001371623.1 | c.109-28T>C | intron_variant | ENST00000643257.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCOF1 | ENST00000643257.2 | c.109-28T>C | intron_variant | NM_001371623.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00154 AC: 235AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000402 AC: 101AN: 251440Hom.: 0 AF XY: 0.000331 AC XY: 45AN XY: 135916
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GnomAD4 exome AF: 0.000180 AC: 263AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.000186 AC XY: 135AN XY: 727186
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GnomAD4 genome AF: 0.00156 AC: 237AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.00158 AC XY: 118AN XY: 74464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Treacher Collins syndrome 1 Benign:1
Likely benign, no assertion criteria provided | not provided | Genetics Laboratories, Oxford Radcliffe Hospitals NHS Trust | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at