rs11164605
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005263.5(GFI1):c.465C>T(p.Cys155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,558,076 control chromosomes in the GnomAD database, including 527,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.85 ( 55359 hom., cov: 34)
Exomes 𝑓: 0.82 ( 472346 hom. )
Consequence
GFI1
NM_005263.5 synonymous
NM_005263.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.199
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 1-92480922-G-A is Benign according to our data. Variant chr1-92480922-G-A is described in ClinVar as [Benign]. Clinvar id is 211078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-92480922-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=0.199 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GFI1 | NM_005263.5 | c.465C>T | p.Cys155= | synonymous_variant | 4/7 | ENST00000294702.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFI1 | ENST00000294702.6 | c.465C>T | p.Cys155= | synonymous_variant | 4/7 | 2 | NM_005263.5 | P1 | |
GFI1 | ENST00000370332.5 | c.465C>T | p.Cys155= | synonymous_variant | 4/7 | 1 | P1 | ||
GFI1 | ENST00000427103.6 | c.465C>T | p.Cys155= | synonymous_variant | 4/7 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.851 AC: 129171AN: 151846Hom.: 55303 Cov.: 34
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GnomAD3 exomes AF: 0.862 AC: 133337AN: 154688Hom.: 57823 AF XY: 0.865 AC XY: 72878AN XY: 84290
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GnomAD4 exome AF: 0.818 AC: 1149886AN: 1406116Hom.: 472346 Cov.: 60 AF XY: 0.822 AC XY: 570637AN XY: 694522
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GnomAD4 genome ? AF: 0.851 AC: 129287AN: 151960Hom.: 55359 Cov.: 34 AF XY: 0.853 AC XY: 63355AN XY: 74272
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ClinVar
Significance: Benign
Submissions summary: Benign:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 17, 2015 | - - |
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:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
not provided Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
Computational scores
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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