rs3832728

Variant names:

• chr11-47358725-GCACA-G
• rs3832728
• ENST00000533968.1:c.608_611delTGTG

Your query was ambiguous. Multiple possible variants found:

• chr11-47358725-GCACA-G
• chr11-47358725-GCACA-GCA
• chr11-47358725-GCACA-GCACACA
• chr11-47358725-GCACA-GCACACACA
• chr11-47358725-GCACA-GCACACACACA
• chr11-47358725-GCACA-GCACACACACACACACTGGCAAACATTCACA

Variant summary

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

The ENST00000533968.1(SPI1):​c.608_611delTGTG​(p.Val203AlafsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000455 in 943,384 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 27)
  • Exomes 𝑓: 0.00023 (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 0.176 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (243/151014) while in subpopulation AFR AF= 0.00557 (229/41142). AF 95% confidence interval is 0.00497. There are 1 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.493+115_493+118delTGTG		intron_variant	Intron 4 of 4	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.496+115_496+118delTGTG		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.608_611delTGTG	p.Val203AlafsTer24	frameshift_variant	Exon 4 of 4	1		ENSP00000438846.1
SPI1	ENST00000378538.8	c.493+115_493+118delTGTG		intron_variant	Intron 4 of 4	1	NM_003120.3	ENSP00000367799.4
SPI1	ENST00000227163.8	c.496+115_496+118delTGTG		intron_variant	Intron 4 of 4	2		ENSP00000227163.4
SPI1	ENST00000533030.1	c.46-3183_46-3180delTGTG		intron_variant	Intron 1 of 1	2		ENSP00000443865.1

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 241 AN: 150902 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00553

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000593

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.000477 AC: 58 AN: 121646 Hom.: 0 AF XY: 0.000350 AC XY: 23 AN XY: 65788

Gnomad AFR exome AF: 0.00756

Gnomad AMR exome AF: 0.000394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000655

Gnomad OTH exome AF: 0.000270

GnomAD4 exome AF: 0.000235 AC: 186 AN: 792370 Hom.: 0 AF XY: 0.000170 AC XY: 70 AN XY: 411674

Gnomad4 AFR exome AF: 0.00634

Gnomad4 AMR exome AF: 0.000322

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000720

Gnomad4 OTH exome AF: 0.000289

GnomAD4 genome AF: 0.00161 AC: 243 AN: 151014 Hom.: 1 Cov.: 27 AF XY: 0.00149 AC XY: 110 AN XY: 73720

Gnomad4 AFR AF: 0.00557

Gnomad4 AMR AF: 0.000592

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000141 Hom.: 95

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;