11-47369488-C-T

Position:

• chr11-47369488-C-T

Variant summary

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

The NM_003120.3(SPI1):​c.142+6145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 149,736 control chromosomes in the GnomAD database, including 35,935 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 (35935 hom., cov: 25)
• Consequence: SPI1 NM_003120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPI1	NM_003120.3	c.142+6145G>A		intron_variant		ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.145+6145G>A		intron_variant			NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8	c.142+6145G>A		intron_variant		1	NM_003120.3	ENSP00000367799	P4

Frequencies

GnomAD3 genomes AF: 0.691 AC: 103435 AN: 149628 Hom.: 35903 Cov.: 25

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.691 AC: 103507 AN: 149736 Hom.: 35935 Cov.: 25 AF XY: 0.690 AC XY: 50298 AN XY: 72926

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.660

Alfa AF: 0.675 Hom.: 16678

Bravo AF: 0.689

Asia WGS AF: 0.677 AC: 2350 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.38

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: rs10769258; hg19: chr11-47391039; COSMIC: COSV57045973;