chr1-92478757-C-CAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005263.5(GFI1):​c.925-6_925-5dupCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 949 hom., cov: 0)
Exomes 𝑓: 0.066 ( 53 hom. )

Consequence

GFI1
NM_005263.5 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

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 Benign. Variant got -16 ACMG points.

BP6
Variant 1-92478757-C-CAG is Benign according to our data. Variant chr1-92478757-C-CAG is described in ClinVar as [Likely_benign]. Clinvar id is 402897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GFI1NM_005263.5 linkc.925-6_925-5dupCT 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.925-5_925-4insCT splice_region_variant, intron_variant Intron 5 of 6 2 NM_005263.5 ENSP00000294702.5 Q99684
GFI1ENST00000370332.5 linkc.925-5_925-4insCT splice_region_variant, intron_variant Intron 5 of 6 1 ENSP00000359357.1 Q99684
GFI1ENST00000427103.6 linkc.925-5_925-4insCT splice_region_variant, intron_variant Intron 5 of 6 1 ENSP00000399719.1 Q99684
GFI1ENST00000696667.1 linkc.138+1590_138+1591insCT intron_variant Intron 1 of 1 ENSP00000512792.1 A0A8Q3SIQ6

Frequencies

GnomAD3 genomes
AF:
0.0978
AC:
13491
AN:
137960
Hom.:
948
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.197
Gnomad AMI
AF:
0.0142
Gnomad AMR
AF:
0.0944
Gnomad ASJ
AF:
0.0625
Gnomad EAS
AF:
0.0933
Gnomad SAS
AF:
0.0569
Gnomad FIN
AF:
0.0640
Gnomad MID
AF:
0.103
Gnomad NFE
AF:
0.0539
Gnomad OTH
AF:
0.0912
GnomAD4 exome
AF:
0.0659
AC:
88579
AN:
1344604
Hom.:
53
Cov.:
0
AF XY:
0.0661
AC XY:
44126
AN XY:
667500
show subpopulations
Gnomad4 AFR exome
AF:
0.172
Gnomad4 AMR exome
AF:
0.0821
Gnomad4 ASJ exome
AF:
0.0599
Gnomad4 EAS exome
AF:
0.125
Gnomad4 SAS exome
AF:
0.0792
Gnomad4 FIN exome
AF:
0.0584
Gnomad4 NFE exome
AF:
0.0594
Gnomad4 OTH exome
AF:
0.0720
GnomAD4 genome
AF:
0.0978
AC:
13498
AN:
138066
Hom.:
949
Cov.:
0
AF XY:
0.0973
AC XY:
6451
AN XY:
66332
show subpopulations
Gnomad4 AFR
AF:
0.197
Gnomad4 AMR
AF:
0.0943
Gnomad4 ASJ
AF:
0.0625
Gnomad4 EAS
AF:
0.0919
Gnomad4 SAS
AF:
0.0573
Gnomad4 FIN
AF:
0.0640
Gnomad4 NFE
AF:
0.0539
Gnomad4 OTH
AF:
0.0917

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Mar 29, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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 -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

GFI1-related disorder Benign:1
Jul 12, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Jan 27, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nonimmune chronic idiopathic neutropenia of adults;C2751288:Neutropenia, severe congenital, 2, autosomal dominant Benign:1
Aug 24, 2021
Fulgent Genetics, Fulgent Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35896485; hg19: chr1-92944314; API