Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005263.5(GFI1):c.-7G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,550,276 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00030 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

GFI1
NM_005263.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.344

Publications

1 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-92483494-C-T is Benign according to our data. Variant chr1-92483494-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 259697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005263.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GFI1	NM_005263.5	MANE Select	c.-7G>A	5_prime_UTR	Exon 2 of 7	NP_005254.2
GFI1	NM_001127215.3		c.-7G>A	5_prime_UTR	Exon 2 of 7	NP_001120687.1
GFI1	NM_001127216.3		c.-7G>A	5_prime_UTR	Exon 2 of 7	NP_001120688.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GFI1	ENST00000294702.6	TSL:2 MANE Select	c.-7G>A	5_prime_UTR	Exon 2 of 7	ENSP00000294702.5
GFI1	ENST00000370332.5	TSL:1	c.-7G>A	5_prime_UTR	Exon 2 of 7	ENSP00000359357.1
GFI1	ENST00000427103.6	TSL:1	c.-7G>A	5_prime_UTR	Exon 2 of 7	ENSP00000399719.1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000323

AC:

AN:

229396

AF XY:

0.000313

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.000893

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000586

Gnomad OTH exome

AF:

0.000699

GnomAD4 exome

AF:

0.000187

AC:

262

AN:

1397942

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

135

AN XY:

698090

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32128

American (AMR)

AF:

0.000115

AC:

AN:

43506

Ashkenazi Jewish (ASJ)

AF:

0.00601

AC:

154

AN:

25634

East Asian (EAS)

AF:

0.000516

AC:

AN:

38776

South Asian (SAS)

AF:

0.0000359

AC:

AN:

83670

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52452

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1057966

Other (OTH)

AF:

0.000705

AC:

AN:

58170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000302

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41566

American (AMR)

AF:

0.000196

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000537

Hom.:

Bravo

AF:

0.000219

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.4

(source)

DANN

Benign

0.80

PhyloP100

-0.34

PromoterAI

0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism

(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.

rs184691209

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over