11-47369488-C-T

Variant names:

• chr11-47369488-C-T
• rs10769258
• NM_003120.3:c.142+6145G>A

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+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
• Publications: 32 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: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.142+6145G>A		intron_variant	Intron 2 of 4	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.145+6145G>A		intron_variant	Intron 2 of 4		NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8	c.142+6145G>A		intron_variant	Intron 2 of 4	1	NM_003120.3	ENSP00000367799.4

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

African (AFR) AF: 0.770 AC: 31362 AN: 40742

American (AMR) AF: 0.619 AC: 9272 AN: 14988

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2401 AN: 3464

East Asian (EAS) AF: 0.668 AC: 3417 AN: 5112

South Asian (SAS) AF: 0.701 AC: 3318 AN: 4730

European-Finnish (FIN) AF: 0.685 AC: 6723 AN: 9808

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.666 AC: 45061 AN: 67620

Other (OTH) AF: 0.660 AC: 1371 AN: 2078

Alfa AF: 0.677 Hom.: 18714

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
PhyloP100		-0.52
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: rs10769258; hg19: chr11-47391039; COSMIC: COSV57045973;