9-132969648-G-A

Position:

• chr9-132969648-G-A

Variant summary

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

The NM_004188.8(GFI1B):​c.-700-3077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,164 control chromosomes in the GnomAD database, including 49,959 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 0.81 (49959 hom., cov: 32)
• Consequence: GFI1B NM_004188.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFI1B	NM_004188.8	c.-700-3077G>A		intron_variant			NP_004179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFI1B	ENST00000339463.7	c.-700-3077G>A		intron_variant		1		ENSP00000344782.3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 123034 AN: 152046 Hom.: 49916 Cov.: 32

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.858

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.809 AC: 123135 AN: 152164 Hom.: 49959 Cov.: 32 AF XY: 0.812 AC XY: 60374 AN XY: 74390

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.781

Gnomad4 FIN AF: 0.858

Gnomad4 NFE AF: 0.802

Gnomad4 OTH AF: 0.806

Alfa AF: 0.796 Hom.: 107690

Bravo AF: 0.803

Asia WGS AF: 0.723 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.75

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: rs2905072; hg19: chr9-135845035;