1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAG
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1
The NM_005263.5(GFI1):c.925-5_925-4insCTCT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.054 ( 334 hom., cov: 0)
Exomes 𝑓: 0.11 ( 120 hom. )
Consequence
GFI1
NM_005263.5 splice_region, splice_polypyrimidine_tract, intron
NM_005263.5 splice_region, splice_polypyrimidine_tract, 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 -9 ACMG points.
BP6
?
Variant 1-92478757-C-CAGAG is Benign according to our data. Variant chr1-92478757-C-CAGAG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 298179.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFI1 | NM_005263.5 | c.925-5_925-4insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000294702.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFI1 | ENST00000294702.6 | c.925-5_925-4insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_005263.5 | P1 | |||
GFI1 | ENST00000370332.5 | c.925-5_925-4insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
GFI1 | ENST00000427103.6 | c.925-5_925-4insCTCT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | P1 | ||||
GFI1 | ENST00000696667.1 | c.138+1590_138+1591insCTCT | intron_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0539 AC: 7431AN: 137984Hom.: 333 Cov.: 0
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GnomAD4 exome AF: 0.111 AC: 147313AN: 1327218Hom.: 120 Cov.: 0 AF XY: 0.113 AC XY: 74432AN XY: 659168
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GnomAD4 genome ? AF: 0.0539 AC: 7447AN: 138092Hom.: 334 Cov.: 0 AF XY: 0.0536 AC XY: 3555AN XY: 66346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Severe congenital neutropenia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 05, 2021 | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at