Variant 19-50423008-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003121.5(SPIB):c.310G>C(p.Ala104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 1,508,458 control chromosomes in the GnomAD database, including 405,515 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 31479 hom., cov: 27)

Exomes 𝑓: 0.73 ( 374036 hom. )

Consequence

SPIB
NM_003121.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2879312E-6).

BP6

Variant 19-50423008-G-C is Benign according to our data. Variant chr19-50423008-G-C is described in ClinVar as [Benign]. Clinvar id is 769042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPIB	NM_003121.5 linkuse as main transcript	c.310G>C	p.Ala104Pro	missense_variant	4/6	ENST00000595883.6	NP_003112.2	Q01892-1A0A024R4I5
SPIB	NM_001243999.2 linkuse as main transcript	c.310G>C	p.Ala104Pro	missense_variant	4/6		NP_001230928.1	Q01892-2
SPIB	NM_001244000.2 linkuse as main transcript	c.252G>C	p.Leu84Leu	synonymous_variant	4/6		NP_001230929.2	Q01892
SPIB	NM_001243998.2 linkuse as main transcript	c.66+463G>C		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>C	p.Ala104Pro	missense_variant	4/6	1	NM_003121.5	ENSP00000471921.1		Q01892-1
ENSG00000142539	ENST00000599632.1 linkuse as main transcript	c.712G>C	p.Ala238Pro	missense_variant	8/10	5		ENSP00000473233.1		M0R3H8

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92577

AN:

151182

Hom.:

31478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.648

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.611

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.763

Gnomad OTH

AF:

0.600

GnomAD3 exomes

AF:

0.659

AC:

128155

AN:

194396

Hom.:

45482

AF XY:

0.670

AC XY:

71336

AN XY:

106480

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.820

Gnomad NFE exome

AF:

0.763

Gnomad OTH exome

AF:

0.698

GnomAD4 exome

AF:

0.730

AC:

991092

AN:

1357158

Hom.:

374036

Cov.:

AF XY:

0.728

AC XY:

489006

AN XY:

671262

show subpopulations

Gnomad4 AFR exome

AF:

0.320

Gnomad4 AMR exome

AF:

0.657

Gnomad4 ASJ exome

AF:

0.659

Gnomad4 EAS exome

AF:

0.175

Gnomad4 SAS exome

AF:

0.646

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.771

Gnomad4 OTH exome

AF:

0.687

GnomAD4 genome

AF:

0.612

AC:

92618

AN:

151300

Hom.:

31479

Cov.:

AF XY:

0.614

AC XY:

45353

AN XY:

73878

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.648

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.610

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.763

Gnomad4 OTH

AF:

0.603

Alfa

AF:

0.630

Hom.:

4146

Bravo

AF:

0.586

ESP6500AA

AF:

0.300

AC:

1316

ESP6500EA

AF:

0.701

AC:

5995

ExAC

AF:

0.653

AC:

78567

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 30, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.3

DANN

Benign

0.40

DEOGEN2

Benign

0.056

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.76

T;T;T

MetaRNN

Benign

0.0000023

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.42

PROVEAN

Benign

0.46

.;.;N

REVEL

Benign

0.027

Sift

Benign

0.32

.;.;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.0040

B;.;B

Vest4

0.19

MPC

0.041

ClinPred

0.0039

GERP RS

-2.1

Varity_R

0.11

gMVP

0.33

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