ENST00000339463.7:c.-701+10837C>T

Variant names:

• chr9-132956506-C-T
• rs3011289
• ENST00000339463.7:c.-701+10837C>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+10837C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,046 control chromosomes in the GnomAD database, including 34,338 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 0.67 (34338 hom., cov: 32)
• Consequence: GFI1B ENST00000339463.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339463.7. 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.-701+10837C>T		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.-701+10837C>T		intron	N/A	ENSP00000344782.3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 102007 AN: 151926 Hom.: 34297 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.672 AC: 102109 AN: 152046 Hom.: 34338 Cov.: 32 AF XY: 0.671 AC XY: 49903 AN XY: 74318

African (AFR) AF: 0.641 AC: 26571 AN: 41476

American (AMR) AF: 0.651 AC: 9942 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2480 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3430 AN: 5160

South Asian (SAS) AF: 0.768 AC: 3698 AN: 4816

European-Finnish (FIN) AF: 0.634 AC: 6703 AN: 10568

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47140 AN: 67974

Other (OTH) AF: 0.654 AC: 1382 AN: 2114

Alfa AF: 0.681 Hom.: 68085

Bravo AF: 0.667

Asia WGS AF: 0.732 AC: 2545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		0.027
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: rs3011289; hg19: chr9-135831893;