11-47358725-GCACA-GCA

Variant names:

• chr11-47358725-GCA-G
• rs3832728
• ENST00000533968.1:c.610_611delTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_Strong BS1 BS2

The ENST00000533968.1(SPI1):​c.610_611delTG​(p.Cys204HisfsTer51) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 918,092 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0030 (0 hom.)
• Consequence: SPI1 ENST00000533968.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

Genes affected

SPI1 (HGNC:11241): (Spi-1 proto-oncogene) This gene encodes an ETS-domain transcription factor that activates gene expression during myeloid and B-lymphoid cell development. The nuclear protein binds to a purine-rich sequence known as the PU-box found near the promoters of target genes, and regulates their expression in coordination with other transcription factors and cofactors. The protein can also regulate alternative splicing of target genes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.173 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000272 (41/150980) while in subpopulation AMR AF= 0.000724 (11/15196). AF 95% confidence interval is 0.000405. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.493+117_493+118delTG		intron_variant	Intron 4 of 4	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.496+117_496+118delTG		intron_variant	Intron 4 of 4		NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000533968.1	c.610_611delTG	p.Cys204HisfsTer51	frameshift_variant	Exon 4 of 4	1		ENSP00000438846.1
SPI1	ENST00000378538.8	c.493+117_493+118delTG		intron_variant	Intron 4 of 4	1	NM_003120.3	ENSP00000367799.4
SPI1	ENST00000227163.8	c.496+117_496+118delTG		intron_variant	Intron 4 of 4	2		ENSP00000227163.4
SPI1	ENST00000533030.1	c.46-3181_46-3180delTG		intron_variant	Intron 1 of 1	2		ENSP00000443865.1

Frequencies

GnomAD3 genomes AF: 0.000272 AC: 41 AN: 150868 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000725

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000422

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00302 AC: 2313 AN: 767112 Hom.: 0 AF XY: 0.00268 AC XY: 1067 AN XY: 398244

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.000298

Gnomad4 ASJ exome AF: 0.000785

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.000969

Gnomad4 FIN exome AF: 0.000471

Gnomad4 NFE exome AF: 0.00396

Gnomad4 OTH exome AF: 0.00256

GnomAD4 genome AF: 0.000272 AC: 41 AN: 150980 Hom.: 0 Cov.: 27 AF XY: 0.000258 AC XY: 19 AN XY: 73698

Gnomad4 AFR AF: 0.000316

Gnomad4 AMR AF: 0.000724

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000423

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3832728; hg19: chr11-47380276;