rs869116

Positions:

• chr9-132949006-G-A
• chr9-132949006-G-C
• chr9-132949006-G-T

Variant summary

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

The NM_004188.8(GFI1B):​c.-701+3337G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,118 control chromosomes in the GnomAD database, including 14,913 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 0.42 (14913 hom., cov: 33)
• Consequence: GFI1B NM_004188.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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]

GFI1B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GFI1B	NM_004188.8	c.-701+3337G>A		intron_variant			NP_004179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GFI1B	ENST00000339463.7	c.-701+3337G>A		intron_variant		1		ENSP00000344782.3
GFI1B	ENST00000443690.3	n.466+1760G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64536 AN: 151998 Hom.: 14915 Cov.: 33

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.545

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.424 AC: 64552 AN: 152118 Hom.: 14913 Cov.: 33 AF XY: 0.433 AC XY: 32189 AN XY: 74362

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.430

Alfa AF: 0.429 Hom.: 5514

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.52

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: rs869116; hg19: chr9-135824393;