rs7040593

Variant names:

• chr9-132951563-C-T
• rs7040593
• ENST00000339463.7:c.-701+5894C>T

Variant summary

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

The ENST00000339463.7(GFI1B):​c.-701+5894C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0752 in 152,228 control chromosomes in the GnomAD database, including 469 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 0.075 (469 hom., cov: 32)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: GFI1B ENST00000339463.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFI1B	NM_004188.8	c.-701+5894C>T		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+5894C>T		intron_variant	Intron 1 of 10	1		ENSP00000344782.3
GFI1B	ENST00000443690.3	n.821C>T		non_coding_transcript_exon_variant	Exon 4 of 4	5
GFI1B	ENST00000524638.1	n.*10C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11441 AN: 152100 Hom.: 469 Cov.: 32

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0685

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0752 AC: 11448 AN: 152218 Hom.: 469 Cov.: 32 AF XY: 0.0717 AC XY: 5333 AN XY: 74428

African (AFR) AF: 0.0613 AC: 2545 AN: 41500

American (AMR) AF: 0.0684 AC: 1047 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 374 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5186

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4822

European-Finnish (FIN) AF: 0.0503 AC: 534 AN: 10608

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0955 AC: 6496 AN: 68010

Other (OTH) AF: 0.0848 AC: 179 AN: 2112

Alfa AF: 0.0898 Hom.: 1062

Bravo AF: 0.0759

Asia WGS AF: 0.0280 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		-1.6
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: rs7040593; hg19: chr9-135826950;