rs7040593

chr9-132951563-C-T

Variant summary

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

The ENST00000339463.7(GFI1B):c.-701+5894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,228 control chromosomes in the GnomAD database, including 469 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 0.075 (469 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: GFI1B ENST00000339463.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

Genes affected

GFI1B (HGNC:4238): (growth factor independent 1B transcriptional repressor) This gene encodes a zinc-finger containing transcriptional regulator that is primarily expressed in cells of hematopoietic lineage. The encoded protein complexes with numerous other transcriptional regulatory proteins including GATA-1, runt-related transcription factor 1 and histone deacetylases to control expression of genes involved in the development and maturation of erythrocytes and megakaryocytes. Mutations in this gene are the cause of the autosomal dominant platelet disorder, platelet-type bleeding disorder-17. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFI1B	NM_004188.8	c.-701+5894C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFI1B	ENST00000339463.7	c.-701+5894C>T		intron_variant		1		P1
GFI1B	ENST00000443690.3	n.821C>T		non_coding_transcript_exon_variant	4/4	5
GFI1B	ENST00000524638.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11441 AN: 152100 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.0752 AC: 11448 AN: 152218 Hom.: 469 Cov.: 32 AF XY: 0.0717 AC XY: 5333 AN XY: 74428

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.0848

Alfa AF: 0.0915 Hom.: 858

Bravo AF: 0.0759

Asia WGS AF: 0.0280 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.1
Dann	Benign	0.74

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: rs7040593; hg19: chr9-135826950;