rs4752829

Variant names:

• chr11-47375103-G-A
• rs4752829
• NM_003120.3:c.142+530C>T

Variant summary

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

The NM_003120.3(SPI1):​c.142+530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,058 control chromosomes in the GnomAD database, including 8,005 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 0.32 (8005 hom., cov: 33)
• Consequence: SPI1 NM_003120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 16 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: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	NM_003120.3	MANE Select	c.142+530C>T		intron	N/A	NP_003111.2	P17947-1
	SPI1	NM_001080547.2		c.145+530C>T		intron	N/A	NP_001074016.1	P17947-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	ENST00000378538.8	TSL:1 MANE Select	c.142+530C>T		intron	N/A	ENSP00000367799.4	P17947-1
	SPI1	ENST00000533968.1	TSL:1	c.142+530C>T		intron	N/A	ENSP00000438846.1	F5H3K6
	SPI1	ENST00000227163.8	TSL:2	c.145+530C>T		intron	N/A	ENSP00000227163.4	P17947-2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48440 AN: 151940 Hom.: 8003 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.319 AC: 48467 AN: 152058 Hom.: 8005 Cov.: 33 AF XY: 0.323 AC XY: 24025 AN XY: 74328

African (AFR) AF: 0.388 AC: 16093 AN: 41464

American (AMR) AF: 0.308 AC: 4710 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 969 AN: 3462

East Asian (EAS) AF: 0.342 AC: 1766 AN: 5160

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4820

European-Finnish (FIN) AF: 0.394 AC: 4164 AN: 10570

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18897 AN: 67980

Other (OTH) AF: 0.272 AC: 573 AN: 2104

Alfa AF: 0.302 Hom.: 997

Bravo AF: 0.318

Asia WGS AF: 0.267 AC: 925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.32
PhyloP100		0.047
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: rs4752829; hg19: chr11-47396654;