11-47356694-T-C

Variant names:

• chr11-47356694-T-C
• rs3824869
• NM_003120.3:c.494-1148A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003120.3(SPI1):​c.494-1148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 151,830 control chromosomes in the GnomAD database, including 42,815 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 0.74 (42815 hom., cov: 30)
• Consequence: SPI1 NM_003120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 5 publications found

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]

SPI1 Gene-Disease associations (from GenCC):

• agammaglobulinemia 10, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003120.3. 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
	SPI1	NM_003120.3	MANE Select	c.494-1148A>G		intron	N/A	NP_003111.2
	SPI1	NM_001080547.2		c.497-1148A>G		intron	N/A	NP_001074016.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	ENST00000378538.8	TSL:1 MANE Select	c.494-1148A>G		intron	N/A	ENSP00000367799.4
	SPI1	ENST00000227163.8	TSL:2	c.497-1148A>G		intron	N/A	ENSP00000227163.4
	SPI1	ENST00000713542.1		c.494-1152A>G		intron	N/A	ENSP00000518838.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112336 AN: 151712 Hom.: 42743 Cov.: 30

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.721

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.741 AC: 112470 AN: 151830 Hom.: 42815 Cov.: 30 AF XY: 0.746 AC XY: 55341 AN XY: 74216

African (AFR) AF: 0.918 AC: 37972 AN: 41384

American (AMR) AF: 0.762 AC: 11606 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2100 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3802 AN: 5170

South Asian (SAS) AF: 0.720 AC: 3471 AN: 4818

European-Finnish (FIN) AF: 0.746 AC: 7862 AN: 10540

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43391 AN: 67900

Other (OTH) AF: 0.702 AC: 1479 AN: 2108

Alfa AF: 0.678 Hom.: 25949

Bravo AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.25
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3824869; hg19: chr11-47378245;