9-132986611-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001377304.1(GFI1B):c.-20-48T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 886,946 control chromosomes in the GnomAD database, including 54,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7676 hom., cov: 32)
  • Exomes 𝑓: 0.35 (46610 hom.)
• Consequence: GFI1B NM_001377304.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.76

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 9-132986611-T-G is Benign according to our data. Variant chr9-132986611-T-G is described in ClinVar as [Benign]. Clinvar id is 1261847.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFI1B	NM_001377304.1	c.-20-48T>G		intron_variant		ENST00000372122.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFI1B	ENST00000372122.4	c.-20-48T>G		intron_variant		1	NM_001377304.1	P1
GFI1B	ENST00000339463.7	c.-20-48T>G		intron_variant		1		P1
GFI1B	ENST00000372123.5	c.-20-48T>G		intron_variant		5
GFI1B	ENST00000636137.1	c.-20-48T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44090 AN: 151790 Hom.: 7680 Cov.: 32

Gnomad AFR AF: 0.0919

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.346 AC: 254436 AN: 735038 Hom.: 46610 Cov.: 10 AF XY: 0.339 AC XY: 130970 AN XY: 386830

Gnomad4 AFR exome AF: 0.0861

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.371

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.290 AC: 44081 AN: 151908 Hom.: 7676 Cov.: 32 AF XY: 0.294 AC XY: 21794 AN XY: 74218

Gnomad4 AFR AF: 0.0916

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.343

Alfa AF: 0.356 Hom.: 12217

Bravo AF: 0.285

Asia WGS AF: 0.229 AC: 795 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.12
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073577; hg19: chr9-135861998; COSMIC: COSV59745071; COSMIC: COSV59745071;