Variant rs150506480 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005263.5(GFI1):c.115+10_115+29delGCGCGCGGGCCAGGCGGGGC 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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.82

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:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
GFI1	NM_005263.5 link	c.115+10_115+29delGCGCGCGGGCCAGGCGGGGC		intron_variant		ENST00000294702.6	NP_005254.2	Q99684

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFI1	ENST00000294702.6 link	c.115+10_115+29delGCGCGCGGGCCAGGCGGGGC		intron_variant		2	NM_005263.5	ENSP00000294702.5		Q99684

Frequencies

GnomAD3 genomes

AF:

0.0259

AC:

3934

AN:

152110

Hom.:

130

Cov.:

show subpopulations

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.:

AF XY:

0.00965

AC XY:

1196

AN XY:

123876

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74448

show subpopulations

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.:

Bravo

AF:

0.0307

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

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