11-47358725-GCACA-GCACACACA

Variant names:

• chr11-47358725-G-GCACA
• rs3832728
• ENST00000533968.1:c.608_611dupTGTG

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_611dupTGTG​(p.Met205ValfsTer52) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 943,134 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 0.00023 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00018 (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 0.172 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 = 0.000225 (34/151008) while in subpopulation AFR AF= 0.000583 (24/41142). AF 95% confidence interval is 0.000402. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 34 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.493+115_493+118dupTGTG		intron_variant	Intron 4 of 4	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.496+115_496+118dupTGTG		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_611dupTGTG	p.Met205ValfsTer52	frameshift_variant	Exon 4 of 4	1		ENSP00000438846.1
SPI1	ENST00000378538.8	c.493+115_493+118dupTGTG		intron_variant	Intron 4 of 4	1	NM_003120.3	ENSP00000367799.4
SPI1	ENST00000227163.8	c.496+115_496+118dupTGTG		intron_variant	Intron 4 of 4	2		ENSP00000227163.4
SPI1	ENST00000533030.1	c.46-3183_46-3180dupTGTG		intron_variant	Intron 1 of 1	2		ENSP00000443865.1

Frequencies

GnomAD3 genomes AF: 0.000225 AC: 34 AN: 150896 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000591

Gnomad OTH AF: 0.000480

GnomAD4 exome AF: 0.000175 AC: 139 AN: 792126 Hom.: 0 Cov.: 11 AF XY: 0.000151 AC XY: 62 AN XY: 411552

Gnomad4 AFR exome AF: 0.000762

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000187

Gnomad4 SAS exome AF: 0.0000904

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000161

Gnomad4 OTH exome AF: 0.000473

GnomAD4 genome AF: 0.000225 AC: 34 AN: 151008 Hom.: 0 Cov.: 27 AF XY: 0.000163 AC XY: 12 AN XY: 73718

Gnomad4 AFR AF: 0.000583

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000591

Gnomad4 OTH AF: 0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;