Variant 1-92478757-CAGAGAGAGAGAGAGAGAGAGAG-CAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_005263.5(GFI1):c.925-24_925-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 1,520,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

GFI1
NM_005263.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

GFI1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-92478757-CAGAGAGAGAGAGAGAGAGAG-C is Benign according to our data. Variant chr1-92478757-CAGAGAGAGAGAGAGAGAGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1128817.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFI1	NM_005263.5 linkuse as main transcript	c.925-24_925-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000294702.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
GFI1	ENST00000294702.6 linkuse as main transcript	c.925-24_925-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2	NM_005263.5	P1
GFI1	ENST00000370332.5 linkuse as main transcript	c.925-24_925-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		P1
GFI1	ENST00000427103.6 linkuse as main transcript	c.925-24_925-5del	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		P1
GFI1	ENST00000696667.1 linkuse as main transcript	c.138+1571_138+1590del	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

138180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000781

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000709

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:

0.0000239

AC:

AN:

1382644

Hom.:

AF XY:

0.0000175

AC XY:

AN XY:

686992

show subpopulations

Gnomad4 AFR exome

AF:

0.000859

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:

0.00000188

Gnomad4 OTH exome

AF:

0.0000697

GnomAD4 genome

AF:

0.000210

AC:

AN:

138290

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

AN XY:

66446

show subpopulations

Gnomad4 AFR

AF:

0.000778

Gnomad4 AMR

AF:

0.0000708

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

LINK: link

Submissions by phenotype

Neutropenia, severe congenital, 2, autosomal dominant

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 05, 2023

- -

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over