Variant 11-47359042-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003120.3(SPI1):c.331-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,506,956 control chromosomes in the GnomAD database, including 240,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.45 ( 18105 hom., cov: 32)

Exomes 𝑓: 0.57 ( 222333 hom. )

Consequence

SPI1
NM_003120.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.59

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 (BayesDel_noAF=-0.79).

BP6

Variant 11-47359042-G-A is Benign according to our data. Variant chr11-47359042-G-A is described in ClinVar as [Benign]. Clinvar id is 2687976.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3 link	c.331-36C>T		intron_variant	Intron 3 of 4	ENST00000378538.8	NP_003111.2	P17947-1
SPI1	NM_001080547.2 link	c.334-36C>T		intron_variant	Intron 3 of 4		NP_001074016.1	P17947-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPI1	ENST00000378538.8 link	c.331-36C>T	intron_variant	Intron 3 of 4	1	NM_003120.3	ENSP00000367799.4	P17947-1
SPI1	ENST00000533968.1 link	c.331-36C>T	intron_variant	Intron 3 of 3	1		ENSP00000438846.1	F5H3K6
SPI1	ENST00000227163.8 link	c.334-36C>T	intron_variant	Intron 3 of 4	2		ENSP00000227163.4	P17947-2
SPI1	ENST00000533030.1 link	c.46-3496C>T	intron_variant	Intron 1 of 1	2		ENSP00000443865.1	F5GZ94

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68076

AN:

151938

Hom.:

18101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.607

Gnomad AMR

AF:

0.486

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.494

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.590

Gnomad OTH

AF:

0.521

GnomAD3 exomes

AF:

0.516

AC:

77585

AN:

150388

Hom.:

21131

AF XY:

0.530

AC XY:

41933

AN XY:

79054

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.601

Gnomad EAS exome

AF:

0.459

Gnomad SAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.507

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.568

GnomAD4 exome

AF:

0.567

AC:

768422

AN:

1354900

Hom.:

222333

Cov.:

AF XY:

0.569

AC XY:

377000

AN XY:

662542

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.596

Gnomad4 EAS exome

AF:

0.431

Gnomad4 SAS exome

AF:

0.579

Gnomad4 FIN exome

AF:

0.513

Gnomad4 NFE exome

AF:

0.588

Gnomad4 OTH exome

AF:

0.559

GnomAD4 genome

AF:

0.448

AC:

68086

AN:

152056

Hom.:

18105

Cov.:

AF XY:

0.445

AC XY:

33087

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.149

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.593

Gnomad4 FIN

AF:

0.494

Gnomad4 NFE

AF:

0.590

Gnomad4 OTH

AF:

0.528

Alfa

AF:

0.579

Hom.:

31865

Bravo

AF:

0.431

Asia WGS

AF:

0.562

AC:

1959

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 81% of patients studied by a panel of primary immunodeficiencies. Number of patients: 77. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.7

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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