Variant 19-50419939-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003121.5(SPIB):c.24-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000163 in 1,535,908 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts 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 (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

SPIB
NM_003121.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006608

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.257

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058112144).

BP6

Variant 19-50419939-C-T is Benign according to our data. Variant chr19-50419939-C-T is described in ClinVar as [Benign]. Clinvar id is 736583.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
SPIB	NM_003121.5 linkuse as main transcript	c.24-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000595883.6
SPIB	NM_001243998.2 linkuse as main transcript	c.-35-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SPIB	NM_001243999.2 linkuse as main transcript	c.24-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
SPIB	NM_001244000.2 linkuse as main transcript	c.-35-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPIB	ENST00000595883.6 linkuse as main transcript	c.24-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_003121.5	P1	Q01892-1

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000337

AC:

AN:

168958

Hom.:

AF XY:

0.000362

AC XY:

AN XY:

93930

show subpopulations

Gnomad AFR exome

AF:

0.000107

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00537

Gnomad SAS exome

AF:

0.000193

Gnomad FIN exome

AF:

0.0000544

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.000276

GnomAD4 exome

AF:

0.000160

AC:

222

AN:

1383554

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

112

AN XY:

686362

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000670

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00374

Gnomad4 SAS exome

AF:

0.000173

Gnomad4 FIN exome

AF:

0.0000388

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000861

GnomAD4 genome

AF:

0.000190

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00367

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000289

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.8

DANN

Benign

0.89

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.23

MetaRNN

Benign

0.0058

MutationTaster

Benign

1.0

D;D

MVP

0.26

GERP RS

0.032

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.0040

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