1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG

Position:

• chr1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_005263.5(GFI1):​c.925-16_925-5dupCTCTCTCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (55 hom., cov: 0)
  • Exomes 𝑓: 0.012 (52 hom.)
  • Failed GnomAD Quality Control
• Consequence: GFI1 NM_005263.5 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant 1-92478757-C-CAGAGAGAGAGAG is Benign according to our data. Variant chr1-92478757-C-CAGAGAGAGAGAG is described in ClinVar as [Benign]. Clinvar id is 770490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFI1	NM_005263.5	c.925-16_925-5dupCTCTCTCTCTCT		splice_region_variant, intron_variant		ENST00000294702.6	NP_005254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFI1	ENST00000294702.6	c.925-5_925-4insCTCTCTCTCTCT		splice_region_variant, intron_variant		2	NM_005263.5	ENSP00000294702.5
GFI1	ENST00000370332.5	c.925-5_925-4insCTCTCTCTCTCT		splice_region_variant, intron_variant		1		ENSP00000359357.1
GFI1	ENST00000427103.6	c.925-5_925-4insCTCTCTCTCTCT		splice_region_variant, intron_variant		1		ENSP00000399719.1
GFI1	ENST00000696667.1	c.138+1590_138+1591insCTCTCTCTCTCT		intron_variant				ENSP00000512792.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2768 AN: 138090 Hom.: 55 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.00829

Gnomad AMR AF: 0.0140

Gnomad ASJ AF: 0.0128

Gnomad EAS AF: 0.00793

Gnomad SAS AF: 0.0232

Gnomad FIN AF: 0.00548

Gnomad MID AF: 0.0274

Gnomad NFE AF: 0.0186

Gnomad OTH AF: 0.0126

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0122 AC: 16821 AN: 1373868 Hom.: 52 Cov.: 0 AF XY: 0.0122 AC XY: 8321 AN XY: 682484

Gnomad4 AFR exome AF: 0.0229

Gnomad4 AMR exome AF: 0.00830

Gnomad4 ASJ exome AF: 0.00857

Gnomad4 EAS exome AF: 0.00430

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0201 AC: 2772 AN: 138202 Hom.: 55 Cov.: 0 AF XY: 0.0196 AC XY: 1304 AN XY: 66406

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.0140

Gnomad4 ASJ AF: 0.0128

Gnomad4 EAS AF: 0.00794

Gnomad4 SAS AF: 0.0232

Gnomad4 FIN AF: 0.00548

Gnomad4 NFE AF: 0.0186

Gnomad4 OTH AF: 0.0124

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

GFI1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2020

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). -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 01, 2021

- -

Neutropenia, severe congenital, 2, autosomal dominant Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs35896485; hg19: chr1-92944314;