rs780179432

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6

The NM_003120.3(SPI1):c.794G>C(p.Arg265Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,442,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R265Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SPI1
NM_003120.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.51

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

agammaglobulinemia 10, autosomal dominant
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

SPI1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12672585).

BP6

Variant 11-47355246-C-G is Benign according to our data. Variant chr11-47355246-C-G is described in ClinVar as Benign. ClinVar VariationId is 3341195.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003120.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPI1	NM_003120.3	MANE Select	c.794G>C	p.Arg265Pro	missense	Exon 5 of 5	NP_003111.2	P17947-1
	SPI1	NM_001080547.2		c.797G>C	p.Arg266Pro	missense	Exon 5 of 5	NP_001074016.1	P17947-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPI1	ENST00000378538.8	TSL:1 MANE Select	c.794G>C	p.Arg265Pro	missense	Exon 5 of 5	ENSP00000367799.4	P17947-1
SPI1	ENST00000227163.8	TSL:2	c.797G>C	p.Arg266Pro	missense	Exon 5 of 5	ENSP00000227163.4	P17947-2
SPI1	ENST00000713543.1		c.533G>C	p.Arg178Pro	missense	Exon 7 of 7	ENSP00000518839.1	A0AAA9YHK5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152028

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000141

AC:

AN:

70708

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000155

AC:

AN:

1290592

Hom.:

Cov.:

AF XY:

0.00000159

AC XY:

AN XY:

630498

show subpopulations

African (AFR)

AF:

0.0000377

AC:

AN:

26544

American (AMR)

AF:

0.00

AC:

AN:

23856

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20048

East Asian (EAS)

AF:

0.00

AC:

AN:

30612

South Asian (SAS)

AF:

0.00

AC:

AN:

64424

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

9.69e-7

AC:

AN:

1032482

Other (OTH)

AF:

0.00

AC:

AN:

53372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74256

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67968

Other (OTH)

AF:

0.00

AC:

AN:

2088

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000913

AC:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Agammaglobulinemia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

2.5

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.3

REVEL

Benign

0.082

Sift

Uncertain

0.0050

Sift4G

Benign

0.11

Polyphen

0.35

Vest4

0.27

MutPred

0.28

Loss of catalytic residue at R265 (P = 0.0427)

MVP

0.54

MPC

3.5

ClinPred

0.85

GERP RS

3.0

Varity_R

0.29

gMVP

0.91

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over