rs2905078

Variant names:

• chr9-132965148-G-A
• rs2905078
• ENST00000339463.7:c.-700-7577G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-132965148-G-A
• chr9-132965148-G-T

Variant summary

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

The ENST00000339463.7(GFI1B):​c.-700-7577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,908 control chromosomes in the GnomAD database, including 15,527 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 0.45 (15527 hom., cov: 32)
• Consequence: GFI1B ENST00000339463.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• 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: 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFI1B	NM_004188.8	c.-700-7577G>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.-700-7577G>A		intron_variant	Intron 1 of 10	1		ENSP00000344782.3

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68381 AN: 151790 Hom.: 15517 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.450 AC: 68430 AN: 151908 Hom.: 15527 Cov.: 32 AF XY: 0.451 AC XY: 33529 AN XY: 74266

African (AFR) AF: 0.488 AC: 20213 AN: 41388

American (AMR) AF: 0.443 AC: 6749 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1949 AN: 5174

South Asian (SAS) AF: 0.412 AC: 1983 AN: 4812

European-Finnish (FIN) AF: 0.487 AC: 5147 AN: 10558

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29482 AN: 67948

Other (OTH) AF: 0.420 AC: 885 AN: 2106

Alfa AF: 0.436 Hom.: 28744

Bravo AF: 0.447

Asia WGS AF: 0.367 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.98
DANN	Benign	0.32
PhyloP100		-0.28
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: rs2905078; hg19: chr9-135840535;