Variant chr11-47358725-G-GCA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 4P and 10B. PVS1_StrongBP6_ModerateBA1

The ENST00000533968.1(SPI1):c.610_611dupTG(p.Met205AlafsTer24) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 940,472 control chromosomes in the GnomAD database, including 9,290 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4234 hom., cov: 27)

Exomes 𝑓: 0.15 ( 5056 hom. )

Consequence

SPI1
ENST00000533968.1 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0410

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.172 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 11-47358725-G-GCA is Benign according to our data. Variant chr11-47358725-G-GCA is described in ClinVar as [Benign]. Clinvar id is 2688186.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3 link	c.493+117_493+118dupTG		intron_variant	Intron 4 of 4	ENST00000378538.8	NP_003111.2	P17947-1
SPI1	NM_001080547.2 link	c.496+117_496+118dupTG		intron_variant	Intron 4 of 4		NP_001074016.1	P17947-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPI1	ENST00000533968.1 link	c.610_611dupTG	p.Met205AlafsTer24	frameshift_variant	Exon 4 of 4	1		ENSP00000438846.1	F5H3K6
SPI1	ENST00000378538.8 link	c.493+117_493+118dupTG		intron_variant	Intron 4 of 4	1	NM_003120.3	ENSP00000367799.4	P17947-1
SPI1	ENST00000227163.8 link	c.496+117_496+118dupTG		intron_variant	Intron 4 of 4	2		ENSP00000227163.4	P17947-2
SPI1	ENST00000533030.1 link	c.46-3181_46-3180dupTG		intron_variant	Intron 1 of 1	2		ENSP00000443865.1	F5GZ94

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

32995

AN:

150802

Hom.:

4235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.264

Gnomad MID

AF:

0.166

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.208

AC:

25255

AN:

121646

Hom.:

1381

AF XY:

0.199

AC XY:

13092

AN XY:

65788

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.292

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.322

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.157

GnomAD4 exome

AF:

0.150

AC:

118168

AN:

789558

Hom.:

5056

Cov.:

AF XY:

0.149

AC XY:

61260

AN XY:

410274

show subpopulations

Gnomad4 AFR exome

AF:

0.282

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.345

Gnomad4 SAS exome

AF:

0.170

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.120

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.219

AC:

33004

AN:

150914

Hom.:

4234

Cov.:

AF XY:

0.225

AC XY:

16574

AN XY:

73666

show subpopulations

Gnomad4 AFR

AF:

0.335

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.330

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.264

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.172

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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 39% of patients studied by a panel of primary immunodeficiencies. Number of patients: 37. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over