11-47378311-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_003120.3(SPI1):c.43C>A(p.Pro15Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SPI1
NM_003120.3 missense, splice_region

Scores

Splicing: ADA: 0.004484

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.52

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2229324).

BP6

Variant 11-47378311-G-T is Benign according to our data. Variant chr11-47378311-G-T is described in ClinVar as [Benign]. Clinvar id is 3341210.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPI1	NM_003120.3 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 5	ENST00000378538.8	NP_003111.2	P17947-1
SPI1	NM_001080547.2 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 5		NP_001074016.1	P17947-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPI1	ENST00000378538.8 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 5	1	NM_003120.3	ENSP00000367799.4	P17947-1
SPI1	ENST00000533968.1 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 4	1		ENSP00000438846.1	F5H3K6
SPI1	ENST00000227163.8 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 5	2		ENSP00000227163.4	P17947-2
SPI1	ENST00000533030.1 link	c.43C>A	p.Pro15Thr	missense_variant, splice_region_variant	Exon 1 of 2	2		ENSP00000443865.1	F5GZ94

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248100

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Agammaglobulinemia

Benign:1

Aug 28, 2024

Neil Romberg Laboratory, Children's Hospital of Philadelphia

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;.;.;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.21

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.78

T;T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.22

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.4

M;M;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.1

N;N;D;D

REVEL

Benign

0.059

Sift

Benign

0.075

T;D;.;T

Sift4G

Benign

0.26

T;T;.;T

Polyphen

0.028

B;P;.;D

Vest4

0.23

MutPred

0.41

Gain of phosphorylation at P15 (P = 0.0124);Gain of phosphorylation at P15 (P = 0.0124);Gain of phosphorylation at P15 (P = 0.0124);Gain of phosphorylation at P15 (P = 0.0124);

MVP

0.64

MPC

0.77

ClinPred

0.62

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.098

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0045

dbscSNV1_RF

Benign

0.14

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