rs4752829

Positions:

• chr11-47375103-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPI1	NM_003120.3	c.142+530C>T		intron_variant		ENST00000378538.8
SPI1	NM_001080547.2	c.145+530C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPI1	ENST00000378538.8	c.142+530C>T		intron_variant		1	NM_003120.3	P4

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

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.272

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4752829; hg19: chr11-47396654;