chr9-132949006-G-A

Variant names:

• chr9-132949006-G-A
• rs869116
• ENST00000339463.7:c.-701+3337G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000339463.7(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 ENST00000339463.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• autosomal dominant macrothrombocytopenia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• platelet storage pool deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GFI1B	NM_004188.8	c.-701+3337G>A		intron_variant	Intron 1 of 10		NP_004179.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFI1B	ENST00000339463.7	c.-701+3337G>A		intron_variant	Intron 1 of 10	1		ENSP00000344782.3
GFI1B	ENST00000443690.3	n.466+1760G>A		intron_variant	Intron 3 of 3	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

African (AFR) AF: 0.230 AC: 9541 AN: 41500

American (AMR) AF: 0.440 AC: 6729 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1959 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2814 AN: 5168

South Asian (SAS) AF: 0.599 AC: 2891 AN: 4826

European-Finnish (FIN) AF: 0.543 AC: 5746 AN: 10578

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33401 AN: 67972

Other (OTH) AF: 0.430 AC: 908 AN: 2112

Alfa AF: 0.431 Hom.: 6669

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
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs869116; hg19: chr9-135824393;