chr1-92476059-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_005263.5(GFI1):c.1239G>A(p.Arg413=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,613,998 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 2 hom. )
Consequence
GFI1
NM_005263.5 synonymous
NM_005263.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.82
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 1-92476059-C-T is Benign according to our data. Variant chr1-92476059-C-T is described in ClinVar as [Benign]. Clinvar id is 759202.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-92476059-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.83 with no splicing effect.
BS2
?
High AC in GnomAdExome at 89 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFI1 | NM_005263.5 | c.1239G>A | p.Arg413= | synonymous_variant | 7/7 | ENST00000294702.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFI1 | ENST00000294702.6 | c.1239G>A | p.Arg413= | synonymous_variant | 7/7 | 2 | NM_005263.5 | P1 | |
GFI1 | ENST00000370332.5 | c.1239G>A | p.Arg413= | synonymous_variant | 7/7 | 1 | P1 | ||
GFI1 | ENST00000427103.6 | c.1239G>A | p.Arg413= | synonymous_variant | 7/7 | 1 | P1 | ||
GFI1 | ENST00000696667.1 | c.287G>A | p.Gly96Asp | missense_variant | 2/2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152188Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000354 AC: 89AN: 251078Hom.: 2 AF XY: 0.000258 AC XY: 35AN XY: 135746
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GnomAD4 exome AF: 0.0000746 AC: 109AN: 1461810Hom.: 2 Cov.: 32 AF XY: 0.0000660 AC XY: 48AN XY: 727200
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at