rs150506480

Positions:

• chr1-92483343-AGCCCCGCCTGGCCCGCGCGC-A
• chr1-92483343-AGCCCCGCCTGGCCCGCGCGC-AGCCCCGCCTGGCCCGCGCGCGCCCCGCCTGGCCCGCGCGC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005263.5(GFI1):​c.115+10_115+29del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,285,568 control chromosomes in the GnomAD database, including 271 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (130 hom., cov: 32)
  • Exomes 𝑓: 0.010 (141 hom.)
• Consequence: GFI1 NM_005263.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.82

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 -16 ACMG points.

• BP6: Variant 1-92483343-AGCCCCGCCTGGCCCGCGCGC-A is Benign according to our data. Variant chr1-92483343-AGCCCCGCCTGGCCCGCGCGC-A is described in ClinVar as [Benign]. Clinvar id is 259700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFI1	NM_005263.5	c.115+10_115+29del		intron_variant		ENST00000294702.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFI1	ENST00000294702.6	c.115+10_115+29del		intron_variant		2	NM_005263.5	P1

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3934 AN: 152110 Hom.: 130 Cov.: 32

Gnomad AFR AF: 0.0740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00581

Gnomad OTH AF: 0.0344

GnomAD3 exomes AF: 0.0113 AC: 2575 AN: 227540 Hom.: 57 AF XY: 0.00965 AC XY: 1196 AN XY: 123876

Gnomad AFR exome AF: 0.0826

Gnomad AMR exome AF: 0.0131

Gnomad ASJ exome AF: 0.0158

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000349

Gnomad FIN exome AF: 0.000479

Gnomad NFE exome AF: 0.00735

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0101 AC: 11446 AN: 1133340 Hom.: 141 AF XY: 0.00956 AC XY: 5527 AN XY: 577904

Gnomad4 AFR exome AF: 0.0864

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.000421

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00885

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.0259 AC: 3937 AN: 152228 Hom.: 130 Cov.: 32 AF XY: 0.0246 AC XY: 1831 AN XY: 74448

Gnomad4 AFR AF: 0.0739

Gnomad4 AMR AF: 0.0217

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00581

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0149 Hom.: 12

Bravo AF: 0.0307

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 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: rs150506480; hg19: chr1-92948900;