GeneBe

rs35896485

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005263.5(GFI1):​c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

GFI1
NM_005263.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.17
Variant links:
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GFI1NM_005263.5 linkc.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT splice_region_variant, intron_variant Intron 5 of 6 ENST00000294702.6 NP_005254.2 Q99684

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GFI1ENST00000294702.6 linkc.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT splice_region_variant, intron_variant Intron 5 of 6 2 NM_005263.5 ENSP00000294702.5 Q99684
GFI1ENST00000370332.5 linkc.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT splice_region_variant, intron_variant Intron 5 of 6 1 ENSP00000359357.1 Q99684
GFI1ENST00000427103.6 linkc.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT splice_region_variant, intron_variant Intron 5 of 6 1 ENSP00000399719.1 Q99684
GFI1ENST00000696667.1 linkc.138+1567_138+1590delCTCTCTCTCTCTCTCTCTCTCTCT intron_variant Intron 1 of 1 ENSP00000512792.1 A0A8Q3SIQ6

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
7.23e-7
AC:
1
AN:
1382644
Hom.:
0
AF XY:
0.00000146
AC XY:
1
AN XY:
686992
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-92944314; API