rs11164605

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005263.5(GFI1):c.465C>T(p.Cys155Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 1,558,076 control chromosomes in the GnomAD database, including 527,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55359 hom., cov: 34)

Exomes 𝑓: 0.82 ( 472346 hom. )

Consequence

GFI1
NM_005263.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.199

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

neutropenia, severe congenital, 2, autosomal dominant
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
severe congenital neutropenia
Inheritance: AD Classification: MODERATE Submitted by: Illumina
autosomal dominant severe congenital neutropenia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GFI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-92480922-G-A is Benign according to our data. Variant chr1-92480922-G-A is described in ClinVar as Benign. ClinVar VariationId is 211078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.199 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFI1	NM_005263.5 link	c.465C>T	p.Cys155Cys	synonymous_variant	Exon 4 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.465C>T	p.Cys155Cys	synonymous_variant	Exon 4 of 7	2	NM_005263.5	ENSP00000294702.5	Q99684
GFI1	ENST00000370332.5 link	c.465C>T	p.Cys155Cys	synonymous_variant	Exon 4 of 7	1		ENSP00000359357.1	Q99684
GFI1	ENST00000427103.6 link	c.465C>T	p.Cys155Cys	synonymous_variant	Exon 4 of 7	1		ENSP00000399719.1	Q99684

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129171

AN:

151846

Hom.:

55303

Cov.:

show subpopulations

Gnomad AFR

AF:

0.923

Gnomad AMI

AF:

0.818

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.969

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.766

Gnomad MID

AF:

0.860

Gnomad NFE

AF:

0.799

Gnomad OTH

AF:

0.833

GnomAD2 exomes

AF:

0.862

AC:

133337

AN:

154688

AF XY:

0.865

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.909

Gnomad ASJ exome

AF:

0.882

Gnomad EAS exome

AF:

0.966

Gnomad FIN exome

AF:

0.779

Gnomad NFE exome

AF:

0.799

Gnomad OTH exome

AF:

0.840

GnomAD4 exome

AF:

0.818

AC:

1149886

AN:

1406116

Hom.:

472346

Cov.:

AF XY:

0.822

AC XY:

570637

AN XY:

694522

show subpopulations

African (AFR)

AF:

0.926

AC:

29580

AN:

31952

American (AMR)

AF:

0.906

AC:

33261

AN:

36732

Ashkenazi Jewish (ASJ)

AF:

0.883

AC:

22236

AN:

25188

East Asian (EAS)

AF:

0.975

AC:

35355

AN:

36274

South Asian (SAS)

AF:

0.950

AC:

76271

AN:

80286

European-Finnish (FIN)

AF:

0.776

AC:

37474

AN:

48298

Middle Eastern (MID)

AF:

0.890

AC:

4473

AN:

5026

European-Non Finnish (NFE)

AF:

0.795

AC:

862265

AN:

1084124

Other (OTH)

AF:

0.841

AC:

48971

AN:

58236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

11412

22824

34236

45648

57060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20484

40968

61452

81936

102420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.851

AC:

129287

AN:

151960

Hom.:

55359

Cov.:

AF XY:

0.853

AC XY:

63355

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.923

AC:

38315

AN:

41512

American (AMR)

AF:

0.868

AC:

13271

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.887

AC:

3079

AN:

3470

East Asian (EAS)

AF:

0.969

AC:

5009

AN:

5170

South Asian (SAS)

AF:

0.952

AC:

4594

AN:

4826

European-Finnish (FIN)

AF:

0.766

AC:

8048

AN:

10504

Middle Eastern (MID)

AF:

0.856

AC:

250

AN:

292

European-Non Finnish (NFE)

AF:

0.799

AC:

54208

AN:

67874

Other (OTH)

AF:

0.836

AC:

1767

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1005

2010

3015

4020

5025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.821

Hom.:

18389

Bravo

AF:

0.858

Asia WGS

AF:

0.955

AC:

3318

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 17, 2015

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neutropenia, severe congenital, 2, autosomal dominant

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.58

CADD

Benign

9.2

(source)

DANN

Benign

0.91

PhyloP100

0.20

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over