1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAGAG

Variant names:

• chr1-92478757-CAGAGAGAGAGAGAGAGAG-C
• rs35896485
• NM_005263.5:c.925-22_925-5delCTCTCTCTCTCTCTCTCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005263.5(GFI1):​c.925-22_925-5delCTCTCTCTCTCTCTCTCT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,520,824 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: GFI1 NM_005263.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFI1	NM_005263.5	c.925-22_925-5delCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant	Intron 5 of 6	ENST00000294702.6	NP_005254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFI1	ENST00000294702.6	c.925-22_925-5delCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant	Intron 5 of 6	2	NM_005263.5	ENSP00000294702.5
GFI1	ENST00000370332.5	c.925-22_925-5delCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant	Intron 5 of 6	1		ENSP00000359357.1
GFI1	ENST00000427103.6	c.925-22_925-5delCTCTCTCTCTCTCTCTCT		splice_region_variant, intron_variant	Intron 5 of 6	1		ENSP00000399719.1
GFI1	ENST00000696667.1	c.138+1573_138+1590delCTCTCTCTCTCTCTCTCT		intron_variant	Intron 1 of 1			ENSP00000512792.1

Frequencies

GnomAD3 genomes AF: 0.0000145 AC: 2 AN: 138180 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000309

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000101 AC: 14 AN: 1382644 Hom.: 0 AF XY: 0.0000131 AC XY: 9 AN XY: 686992

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000400

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000122

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000145 AC: 2 AN: 138180 Hom.: 0 Cov.: 0 AF XY: 0.0000151 AC XY: 1 AN XY: 66324

Gnomad4 AFR AF: 0.00

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: 0.0000309

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;