11-47358510-A-C

Position:

• chr11-47358510-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000533968.1(SPI1):​c.*89T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 663,600 control chromosomes in the GnomAD database, including 153,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (36868 hom., cov: 31)
  • Exomes 𝑓: 0.67 (116990 hom.)
• Consequence: SPI1 ENST00000533968.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.792

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 11-47358510-A-C is Benign according to our data. Variant chr11-47358510-A-C is described in ClinVar as [Benign]. Clinvar id is 2688018.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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	UniProt
SPI1	NM_003120.3	c.493+334T>G		intron_variant		ENST00000378538.8
SPI1	NM_001080547.2	c.496+334T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPI1	ENST00000378538.8	c.493+334T>G		intron_variant		1	NM_003120.3	P4

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105532 AN: 151728 Hom.: 36836 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.671

GnomAD4 exome AF: 0.675 AC: 345282 AN: 511754 Hom.: 116990 Cov.: 0 AF XY: 0.677 AC XY: 184147 AN XY: 271932

Gnomad4 AFR exome AF: 0.767

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.681

Gnomad4 EAS exome AF: 0.653

Gnomad4 SAS exome AF: 0.720

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.673

GnomAD4 genome AF: 0.695 AC: 105607 AN: 151846 Hom.: 36868 Cov.: 31 AF XY: 0.694 AC XY: 51505 AN XY: 74230

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.663

Alfa AF: 0.668 Hom.: 10483

Bravo AF: 0.694

Asia WGS AF: 0.682 AC: 2369 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.7
DANN	Benign	0.75

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: rs10734557; hg19: chr11-47380061;