chr9-132969648-G-A

Variant names:

• chr9-132969648-G-A
• rs2905072
• ENST00000339463.7:c.-700-3077G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004188.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFI1B	NM_004188.8		c.-700-3077G>A		intron	N/A	NP_004179.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFI1B	ENST00000339463.7	TSL:1	c.-700-3077G>A		intron	N/A	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

African (AFR) AF: 0.841 AC: 34903 AN: 41502

American (AMR) AF: 0.777 AC: 11868 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2932 AN: 3472

East Asian (EAS) AF: 0.685 AC: 3531 AN: 5158

South Asian (SAS) AF: 0.781 AC: 3766 AN: 4822

European-Finnish (FIN) AF: 0.858 AC: 9099 AN: 10604

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54513 AN: 68008

Other (OTH) AF: 0.806 AC: 1703 AN: 2112

Alfa AF: 0.801 Hom.: 232872

Bravo AF: 0.803

Asia WGS AF: 0.723 AC: 2517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.75
PhyloP100		-0.74
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: rs2905072; hg19: chr9-135845035;