NM_003120.3:c.801C>T

Variant names:

• chr11-47355239-G-A
• rs899122071
• NM_003120.3:c.801C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003120.3(SPI1):​c.801C>T​(p.His267His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SPI1 NM_003120.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.97
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=2.97 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3	c.801C>T	p.His267His	synonymous_variant	Exon 5 of 5	ENST00000378538.8	NP_003111.2
SPI1	NM_001080547.2	c.804C>T	p.His268His	synonymous_variant	Exon 5 of 5		NP_001074016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPI1	ENST00000378538.8	c.801C>T	p.His267His	synonymous_variant	Exon 5 of 5	1	NM_003120.3	ENSP00000367799.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275740 Hom.: 0 Cov.: 31 AF XY: 0.00000161 AC XY: 1 AN XY: 622134

African (AFR) AF: 0.00 AC: 0 AN: 25950

American (AMR) AF: 0.00 AC: 0 AN: 21872

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19428

East Asian (EAS) AF: 0.00 AC: 0 AN: 30102

South Asian (SAS) AF: 0.00 AC: 0 AN: 61772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32828

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1025808

Other (OTH) AF: 0.00 AC: 0 AN: 52732

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		3.0

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

Other links and lift over

dbSNP: rs899122071; hg19: chr11-47376790;