9-132989877-GAC-AAT

Variant names:

• chr9-132989877-GAC-AAT
• NM_001377304.1:c.784_786delGACinsAAT
• GFI1B p.Asp262Asn

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PS1 PP3

The NM_001377304.1(GFI1B):​c.784_786delGACinsAAT​(p.Asp262Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Pathogenic in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GFI1B NM_001377304.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.11
• Publications: 0 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: Labcorp Genetics (formerly Invitae), ClinGen
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PS1: Transcript NM_001377304.1 (GFI1B) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377304.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFI1B	NM_001377304.1	MANE Select	c.784_786delGACinsAAT	p.Asp262Asn	missense	N/A	NP_001364233.1	Q5VTD9-1
	GFI1B	NM_001371908.1		c.850_852delGACinsAAT	p.Asp284Asn	missense	N/A	NP_001358837.1	A0A024R8F3
	GFI1B	NM_004188.8		c.784_786delGACinsAAT	p.Asp262Asn	missense	N/A	NP_004179.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFI1B	ENST00000372122.4	TSL:1 MANE Select	c.784_786delGACinsAAT	p.Asp262Asn	missense	N/A	ENSP00000361195.1	Q5VTD9-1
	GFI1B	ENST00000339463.7	TSL:1	c.784_786delGACinsAAT	p.Asp262Asn	missense	N/A	ENSP00000344782.3	Q5VTD9-1
	GFI1B	ENST00000636263.1	TSL:5	c.880_882delGACinsAAT	p.Asp294Asn	missense	N/A	ENSP00000489646.1	A0A1B0GTD0

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-135865264;