chr1-92481581-A-C

Position:

• chr1-92481581-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005263.5(GFI1):​c.299-493T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,086 control chromosomes in the GnomAD database, including 39,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39714 hom., cov: 32)
• Consequence: GFI1 NM_005263.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.933

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFI1	NM_005263.5	c.299-493T>G		intron_variant		ENST00000294702.6	NP_005254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFI1	ENST00000294702.6	c.299-493T>G		intron_variant		2	NM_005263.5	ENSP00000294702	P1
GFI1	ENST00000370332.5	c.299-493T>G		intron_variant		1		ENSP00000359357	P1
GFI1	ENST00000427103.6	c.299-493T>G		intron_variant		1		ENSP00000399719	P1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108767 AN: 151968 Hom.: 39668 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.671

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.716 AC: 108873 AN: 152086 Hom.: 39714 Cov.: 32 AF XY: 0.718 AC XY: 53372 AN XY: 74356

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.627

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.675

Alfa AF: 0.666 Hom.: 10024

Bravo AF: 0.725

Asia WGS AF: 0.883 AC: 3069 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.46

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

Other links and lift over

dbSNP: rs11164607; hg19: chr1-92947138;