1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAG
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2
The NM_005263.5(GFI1):c.925-12_925-5delCTCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,515,336 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)
Exomes 𝑓: 0.011 ( 4 hom. )
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP6
Variant 1-92478757-CAGAGAGAG-C is Benign according to our data. Variant chr1-92478757-CAGAGAGAG-C is described in ClinVar as [Benign]. Clinvar id is 470696.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-92478757-CAGAGAGAG-C is described in Lovd as [Likely_benign]. Variant chr1-92478757-CAGAGAGAG-C is described in Lovd as [Likely_benign]. Variant chr1-92478757-CAGAGAGAG-C is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0115 (15786/1377086) while in subpopulation MID AF= 0.018 (75/4162). AF 95% confidence interval is 0.0166. There are 4 homozygotes in gnomad4_exome. There are 8132 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High AC in GnomAd4 at 173 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GFI1 | ENST00000294702.6 | c.925-12_925-5delCTCTCTCT | splice_region_variant, intron_variant | 2 | NM_005263.5 | ENSP00000294702.5 | ||||
GFI1 | ENST00000370332.5 | c.925-12_925-5delCTCTCTCT | splice_region_variant, intron_variant | 1 | ENSP00000359357.1 | |||||
GFI1 | ENST00000427103.6 | c.925-12_925-5delCTCTCTCT | splice_region_variant, intron_variant | 1 | ENSP00000399719.1 | |||||
GFI1 | ENST00000696667.1 | c.138+1583_138+1590delCTCTCTCT | intron_variant | ENSP00000512792.1 |
Frequencies
GnomAD3 genomes AF: 0.00126 AC: 174AN: 138140Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
174
AN:
138140
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0115 AC: 15786AN: 1377086Hom.: 4 AF XY: 0.0119 AC XY: 8132AN XY: 684258
GnomAD4 exome
AF:
AC:
15786
AN:
1377086
Hom.:
AF XY:
AC XY:
8132
AN XY:
684258
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00125 AC: 173AN: 138250Hom.: 0 Cov.: 0 AF XY: 0.00120 AC XY: 80AN XY: 66426
GnomAD4 genome
AF:
AC:
173
AN:
138250
Hom.:
Cov.:
0
AF XY:
AC XY:
80
AN XY:
66426
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at