1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG

Position:

• chr1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005263.5(GFI1):​c.925-30_925-5dupCTCTCTCTCTCTCTCTCTCTCTCTCT 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 0.0000072 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GFI1 NM_005263.5 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-92478757-C-CAGAGAGAGAGAGAGAGAGAGAGAGAG is Benign according to our data. Variant chr1-92478757-C-CAGAGAGAGAGAGAGAGAGAGAGAGAG is described in ClinVar as [Likely_benign]. Clinvar id is 1616579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFI1	NM_005263.5	c.925-30_925-5dupCTCTCTCTCTCTCTCTCTCTCTCTCT		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.925-30_925-5dupCTCTCTCTCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant		2	NM_005263.5	ENSP00000294702.5
GFI1	ENST00000370332.5	c.925-30_925-5dupCTCTCTCTCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant		1		ENSP00000359357.1
GFI1	ENST00000427103.6	c.925-30_925-5dupCTCTCTCTCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant		1		ENSP00000399719.1
GFI1	ENST00000696667.1	c.138+1565_138+1590dupCTCTCTCTCTCTCTCTCTCTCTCTCT		intron_variant				ENSP00000512792.1

Frequencies

GnomAD3 genomes AF: 0.00000724 AC: 1 AN: 138180 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000279

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000434 AC: 6 AN: 1382642 Hom.: 0 Cov.: 0 AF XY: 0.00000291 AC XY: 2 AN XY: 686990

Gnomad4 AFR exome AF: 0.000159

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.42e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000724 AC: 1 AN: 138180 Hom.: 0 Cov.: 0 AF XY: 0.0000151 AC XY: 1 AN XY: 66324

Gnomad4 AFR AF: 0.0000279

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 14, 2021

- -

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;