GeneBe

rs35896485

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

0 publications found
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]
GFI1 Gene-Disease associations (from GenCC):
  • neutropenia, severe congenital, 2, autosomal dominant
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • severe congenital neutropenia
    Inheritance: AD Classification: MODERATE Submitted by: Illumina
  • autosomal dominant severe congenital neutropenia
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005263.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GFI1
NM_005263.5
MANE Select
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/ANP_005254.2Q99684
GFI1
NM_001127215.3
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/ANP_001120687.1Q99684
GFI1
NM_001127216.3
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/ANP_001120688.1Q99684

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GFI1
ENST00000294702.6
TSL:2 MANE Select
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/AENSP00000294702.5Q99684
GFI1
ENST00000370332.5
TSL:1
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/AENSP00000359357.1Q99684
GFI1
ENST00000427103.6
TSL:1
c.925-28_925-5delCTCTCTCTCTCTCTCTCTCTCTCT
splice_region intron
N/AENSP00000399719.1Q99684

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
African (AFR)
AF:
0.00
AC:
0
AN:
31418
American (AMR)
AF:
0.00
AC:
0
AN:
39120
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25004
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36412
South Asian (SAS)
AF:
0.0000126
AC:
1
AN:
79500
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
47858
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4180
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1061794
Other (OTH)
AF:
0.00
AC:
0
AN:
57358
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs35896485; hg19: chr1-92944314; API