Variant rs11546996 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003121.5(SPIB):c.310G>A(p.Ala104Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000181 in 1,523,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A104P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SPIB
NM_003121.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.797

Variant links:

Genes affected

SPIB (HGNC:11242): (Spi-B transcription factor) The protein encoded by this gene is a transcriptional activator that binds to the PU-box (5'-GAGGAA-3') and acts as a lymphoid-specific enhancer. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

SPIB links:

ENSG00000142539 (HGNC:):

ENSG00000142539 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013177156).

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIB	NM_003121.5 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	4/6	ENST00000595883.6	NP_003112.2	Q01892-1A0A024R4I5
SPIB	NM_001243999.2 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	4/6		NP_001230928.1	Q01892-2
SPIB	NM_001244000.2 linkuse as main transcript	c.252G>A	p.Leu84Leu	synonymous_variant	4/6		NP_001230929.2	Q01892
SPIB	NM_001243998.2 linkuse as main transcript	c.66+463G>A		intron_variant			NP_001230927.1	Q01892-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPIB	ENST00000595883.6 linkuse as main transcript	c.310G>A	p.Ala104Thr	missense_variant	4/6	1	NM_003121.5	ENSP00000471921.1		Q01892-1
ENSG00000142539	ENST00000599632.1 linkuse as main transcript	c.712G>A	p.Ala238Thr	missense_variant	8/10	5		ENSP00000473233.1		M0R3H8

Frequencies

GnomAD3 genomes

AF:

0.000747

AC:

113

AN:

151314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000360

AC:

AN:

194396

Hom.:

AF XY:

0.000282

AC XY:

AN XY:

106480

show subpopulations

Gnomad AFR exome

AF:

0.00256

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000119

AC:

163

AN:

1372538

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

678316

show subpopulations

Gnomad4 AFR exome

AF:

0.00357

Gnomad4 AMR exome

AF:

0.00122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000659

Gnomad4 OTH exome

AF:

0.000124

GnomAD4 genome

AF:

0.000746

AC:

113

AN:

151432

Hom.:

Cov.:

AF XY:

0.000771

AC XY:

AN XY:

73958

show subpopulations

Gnomad4 AFR

AF:

0.00259

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

4146

ExAC

AF:

0.000341

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.2

DANN

Benign

0.58

DEOGEN2

Benign

0.050

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

0.25

.;.;N

REVEL

Benign

0.035

Sift

Benign

0.51

.;.;T

Sift4G

Benign

0.50

T;T;T

Polyphen

0.0

B;.;B

Vest4

0.056

MVP

0.31

MPC

0.023

ClinPred

0.0030

GERP RS

-2.1

Varity_R

0.036

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over