rs1325432

chr1-92475293-G-T

Variant summary

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

The NM_005263.5(GFI1):c.*736C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,440 control chromosomes in the GnomAD database, including 2,055 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 0.16 (2047 hom., cov: 31)
  • Exomes 𝑓: 0.15 (8 hom.)
• Consequence: GFI1 NM_005263.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFI1	NM_005263.5	c.*736C>A		3_prime_UTR_variant	7/7	ENST00000294702.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFI1	ENST00000294702.6	c.*736C>A		3_prime_UTR_variant	7/7	2	NM_005263.5	P1
GFI1	ENST00000370332.5	c.*736C>A		3_prime_UTR_variant	7/7	1		P1
GFI1	ENST00000427103.6	c.*736C>A		3_prime_UTR_variant	7/7	1		P1
GFI1	ENST00000696667.1	c.*636C>A		3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23645 AN: 151944 Hom.: 2048 Cov.: 31

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.148 AC: 56 AN: 378 Hom.: 8 Cov.: 0 AF XY: 0.170 AC XY: 32 AN XY: 188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.268

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.155 AC: 23641 AN: 152062 Hom.: 2047 Cov.: 31 AF XY: 0.160 AC XY: 11883 AN XY: 74322

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.152

Alfa AF: 0.171 Hom.: 1878

Bravo AF: 0.152

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.70
Dann	Benign	0.32

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: rs1325432; hg19: chr1-92940850;