chr11-47359042-G-T

Variant names:

• chr11-47359042-G-T
• rs3740689
• NM_003120.3:c.331-36C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003120.3(SPI1):​c.331-36C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPI1 NM_003120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 28 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: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	NM_003120.3	MANE Select	c.331-36C>A		intron	N/A	NP_003111.2	P17947-1
	SPI1	NM_001080547.2		c.334-36C>A		intron	N/A	NP_001074016.1	P17947-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	ENST00000378538.8	TSL:1 MANE Select	c.331-36C>A		intron	N/A	ENSP00000367799.4	P17947-1
	SPI1	ENST00000533968.1	TSL:1	c.331-36C>A		intron	N/A	ENSP00000438846.1	F5H3K6
	SPI1	ENST00000227163.8	TSL:2	c.334-36C>A		intron	N/A	ENSP00000227163.4	P17947-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1356032 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 663078

African (AFR) AF: 0.00 AC: 0 AN: 30342

American (AMR) AF: 0.00 AC: 0 AN: 27146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19560

East Asian (EAS) AF: 0.00 AC: 0 AN: 38510

South Asian (SAS) AF: 0.00 AC: 0 AN: 68568

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5000

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1062774

Other (OTH) AF: 0.00 AC: 0 AN: 55828

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 42230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		2.6
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

Other links and lift over

dbSNP: rs3740689; hg19: chr11-47380593;