Variant chr11-47358789-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000533968.1(SPI1):c.548C>A(p.Ala183Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,528,708 control chromosomes in the GnomAD database, including 245,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 28185 hom., cov: 32)

Exomes 𝑓: 0.56 ( 217518 hom. )

Consequence

SPI1
ENST00000533968.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.33

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4773543E-6).

BP6

Variant 11-47358789-G-T is Benign according to our data. Variant chr11-47358789-G-T is described in ClinVar as [Benign]. Clinvar id is 2687986.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPI1	NM_003120.3 linkuse as main transcript	c.493+55C>A		intron_variant		ENST00000378538.8
SPI1	NM_001080547.2 linkuse as main transcript	c.496+55C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPI1	ENST00000378538.8 linkuse as main transcript	c.493+55C>A		intron_variant		1	NM_003120.3	P4	P17947-1

Frequencies

GnomAD3 genomes

AF:

0.603

AC:

91473

AN:

151648

Hom.:

28149

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.583

GnomAD3 exomes

AF:

0.586

AC:

83189

AN:

141996

Hom.:

24717

AF XY:

0.587

AC XY:

44965

AN XY:

76598

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.560

Gnomad ASJ exome

AF:

0.572

Gnomad EAS exome

AF:

0.678

Gnomad SAS exome

AF:

0.652

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.560

AC:

771335

AN:

1376940

Hom.:

217518

Cov.:

AF XY:

0.562

AC XY:

382108

AN XY:

680118

show subpopulations

Gnomad4 AFR exome

AF:

0.736

Gnomad4 AMR exome

AF:

0.555

Gnomad4 ASJ exome

AF:

0.576

Gnomad4 EAS exome

AF:

0.635

Gnomad4 SAS exome

AF:

0.650

Gnomad4 FIN exome

AF:

0.539

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.567

GnomAD4 genome

AF:

0.603

AC:

91555

AN:

151768

Hom.:

28185

Cov.:

AF XY:

0.603

AC XY:

44717

AN XY:

74152

show subpopulations

Gnomad4 AFR

AF:

0.733

Gnomad4 AMR

AF:

0.545

Gnomad4 ASJ

AF:

0.572

Gnomad4 EAS

AF:

0.654

Gnomad4 SAS

AF:

0.645

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.577

Alfa

AF:

0.483

Hom.:

2404

Bravo

AF:

0.609

TwinsUK

AF:

0.544

AC:

2016

ALSPAC

AF:

0.547

AC:

2107

ExAC

AF:

0.368

AC:

17958

Asia WGS

AF:

0.634

AC:

2201

AN:

3478

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 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.034

DANN

Benign

0.30

DEOGEN2

Benign

0.068

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0000015

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P;P

PROVEAN

Benign

0.060

REVEL

Benign

0.076

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.030

Polyphen

0.16

Vest4

0.068

ClinPred

0.011

GERP RS

-5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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