rs80337126

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_005263.5(GFI1):c.1047C>T(p.Phe349Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0196 in 1,613,968 control chromosomes in the GnomAD database, including 368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 25 hom., cov: 32)

Exomes 𝑓: 0.020 ( 343 hom. )

Consequence

GFI1
NM_005263.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.92

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 Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 1-92478631-G-A is Benign according to our data. Variant chr1-92478631-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0132 (2010/152170) while in subpopulation NFE AF= 0.0212 (1442/68004). AF 95% confidence interval is 0.0203. There are 25 homozygotes in gnomad4. There are 960 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2010 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFI1	NM_005263.5 link	c.1047C>T	p.Phe349Phe	synonymous_variant	Exon 6 of 7	ENST00000294702.6	NP_005254.2	Q99684

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GFI1	ENST00000294702.6 link	c.1047C>T	p.Phe349Phe	synonymous_variant	Exon 6 of 7	2	NM_005263.5	ENSP00000294702.5	Q99684
GFI1	ENST00000370332.5 link	c.1047C>T	p.Phe349Phe	synonymous_variant	Exon 6 of 7	1		ENSP00000359357.1	Q99684
GFI1	ENST00000427103.6 link	c.1047C>T	p.Phe349Phe	synonymous_variant	Exon 6 of 7	1		ENSP00000399719.1	Q99684
GFI1	ENST00000696667.1 link	c.138+1717C>T		intron_variant	Intron 1 of 1			ENSP00000512792.1	A0A8Q3SIQ6

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

2011

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00379

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00989

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0137

AC:

3451

AN:

251492

Hom.:

AF XY:

0.0140

AC XY:

1906

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.00610

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0107

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0206

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0203

AC:

29670

AN:

1461798

Hom.:

343

Cov.:

AF XY:

0.0200

AC XY:

14545

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00305

Gnomad4 AMR exome

AF:

0.00615

Gnomad4 ASJ exome

AF:

0.00673

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0234

Gnomad4 OTH exome

AF:

0.0195

GnomAD4 genome

AF:

0.0132

AC:

2010

AN:

152170

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

960

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00378

Gnomad4 AMR

AF:

0.00988

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0143

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0197

EpiControl

AF:

0.0202

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

GFI1-related disorder

Benign:1

Aug 11, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Neutropenia, severe congenital, 2, autosomal dominant

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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