1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong
The NM_005263.5(GFI1):c.925-16_925-5dupCTCTCTCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.020 ( 55 hom., cov: 0)
Exomes 𝑓: 0.012 ( 52 hom. )
Failed GnomAD Quality Control
Consequence
GFI1
NM_005263.5 splice_region, intron
NM_005263.5 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.17
Genes affected
GFI1 (HGNC:4237): (growth factor independent 1 transcriptional repressor) This gene encodes a nuclear zinc finger protein that functions as a transcriptional repressor. This protein plays a role in diverse developmental contexts, including hematopoiesis and oncogenesis. It functions as part of a complex along with other cofactors to control histone modifications that lead to silencing of the target gene promoters. Mutations in this gene cause autosomal dominant severe congenital neutropenia, and also dominant nonimmune chronic idiopathic neutropenia of adults, which are heterogeneous hematopoietic disorders that cause predispositions to leukemias and infections. Multiple alternatively spliced variants, encoding the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP6
Variant 1-92478757-C-CAGAGAGAGAGAG is Benign according to our data. Variant chr1-92478757-C-CAGAGAGAGAGAG is described in ClinVar as [Benign]. Clinvar id is 770490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GFI1 | ENST00000294702.6 | c.925-5_925-4insCTCTCTCTCTCT | splice_region_variant, intron_variant | 2 | NM_005263.5 | ENSP00000294702.5 | ||||
GFI1 | ENST00000370332.5 | c.925-5_925-4insCTCTCTCTCTCT | splice_region_variant, intron_variant | 1 | ENSP00000359357.1 | |||||
GFI1 | ENST00000427103.6 | c.925-5_925-4insCTCTCTCTCTCT | splice_region_variant, intron_variant | 1 | ENSP00000399719.1 | |||||
GFI1 | ENST00000696667.1 | c.138+1590_138+1591insCTCTCTCTCTCT | intron_variant | ENSP00000512792.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2768AN: 138090Hom.: 55 Cov.: 0 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0122 AC: 16821AN: 1373868Hom.: 52 Cov.: 0 AF XY: 0.0122 AC XY: 8321AN XY: 682484
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0201 AC: 2772AN: 138202Hom.: 55 Cov.: 0 AF XY: 0.0196 AC XY: 1304AN XY: 66406
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
GFI1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 01, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 01, 2021 | - - |
Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 16, 2024 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at