chr11-47356694-T-C

Position:

• chr11-47356694-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPI1	NM_003120.3	c.494-1148A>G		intron_variant		ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.497-1148A>G		intron_variant			NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8	c.494-1148A>G		intron_variant		1	NM_003120.3	ENSP00000367799	P4

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

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.735

Gnomad4 SAS AF: 0.720

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.702

Alfa AF: 0.687 Hom.: 16801

Bravo AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.25
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: rs3824869; hg19: chr11-47378245;