rs1057233

Positions:

• chr11-47354897-G-A
• chr11-47354897-G-C
• chr11-47354897-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003120.3(SPI1):​c.*330C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 238,742 control chromosomes in the GnomAD database, including 55,669 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 0.69 (36049 hom., cov: 29)
  • Exomes 𝑓: 0.66 (19620 hom.)
• Consequence: SPI1 NM_003120.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPI1	NM_003120.3	c.*330C>T		3_prime_UTR_variant	5/5	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.*330C>T		3_prime_UTR_variant	5/5		NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538	c.*330C>T		3_prime_UTR_variant	5/5	1	NM_003120.3	ENSP00000367799.4
SPI1	ENST00000227163.8	c.*330C>T		downstream_gene_variant		2		ENSP00000227163.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104420 AN: 151702 Hom.: 36018 Cov.: 29

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.665

GnomAD4 exome AF: 0.665 AC: 57768 AN: 86922 Hom.: 19620 Cov.: 0 AF XY: 0.665 AC XY: 29461 AN XY: 44302

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.619

Gnomad4 ASJ exome AF: 0.675

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.666

Gnomad4 OTH exome AF: 0.669

GnomAD4 genome AF: 0.688 AC: 104495 AN: 151820 Hom.: 36049 Cov.: 29 AF XY: 0.687 AC XY: 50967 AN XY: 74162

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.658

Alfa AF: 0.663 Hom.: 11497

Bravo AF: 0.685

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1057233; hg19: chr11-47376448;