Variant chr17-54999625-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The ENST00000398391.6(STXBP4):c.57-1G>A variant causes a splice acceptor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 1,608,732 control chromosomes in the GnomAD database, including 423,129 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39303 hom., cov: 32)

Exomes 𝑓: 0.72 ( 383826 hom. )

Consequence

STXBP4
ENST00000398391.6 splice_acceptor

Scores

Splicing: ADA: 0.0003532

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

Variant links:

Genes affected

STXBP4 (HGNC:19694): (syntaxin binding protein 4) Enables syntaxin binding activity. Involved in several processes, including positive regulation of cell cycle G1/S phase transition; positive regulation of keratinocyte proliferation; and protein stabilization. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

STXBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.29268292 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.3, offset of 6, new splice context is: tgatttctttttaatactAGgtt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP4	NM_178509.6 linkuse as main transcript	c.288-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000376352.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
STXBP4	ENST00000398391.6 linkuse as main transcript	c.57-1G>A	splice_acceptor_variant	1			Q6ZWJ1-2
STXBP4	ENST00000376352.6 linkuse as main transcript	c.288-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2	NM_178509.6	P1	Q6ZWJ1-1
STXBP4	ENST00000434978.6 linkuse as main transcript	c.288-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1
STXBP4	ENST00000405898.5 linkuse as main transcript	c.288-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.717

AC:

108872

AN:

151930

Hom.:

39256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.660

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.766

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.908

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.726

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.713

Gnomad OTH

AF:

0.699

GnomAD3 exomes

AF:

0.757

AC:

187246

AN:

247348

Hom.:

71563

AF XY:

0.757

AC XY:

101271

AN XY:

133746

show subpopulations

Gnomad AFR exome

AF:

0.652

Gnomad AMR exome

AF:

0.843

Gnomad ASJ exome

AF:

0.760

Gnomad EAS exome

AF:

0.894

Gnomad SAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.726

Gnomad NFE exome

AF:

0.716

Gnomad OTH exome

AF:

0.739

GnomAD4 exome

AF:

0.724

AC:

1054201

AN:

1456684

Hom.:

383826

Cov.:

AF XY:

0.727

AC XY:

526723

AN XY:

724752

show subpopulations

Gnomad4 AFR exome

AF:

0.656

Gnomad4 AMR exome

AF:

0.836

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.928

Gnomad4 SAS exome

AF:

0.811

Gnomad4 FIN exome

AF:

0.723

Gnomad4 NFE exome

AF:

0.706

Gnomad4 OTH exome

AF:

0.725

GnomAD4 genome

AF:

0.717

AC:

108983

AN:

152048

Hom.:

39303

Cov.:

AF XY:

0.721

AC XY:

53555

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.661

Gnomad4 AMR

AF:

0.766

Gnomad4 ASJ

AF:

0.756

Gnomad4 EAS

AF:

0.908

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.726

Gnomad4 NFE

AF:

0.713

Gnomad4 OTH

AF:

0.699

Alfa

AF:

0.719

Hom.:

77236

Bravo

AF:

0.716

TwinsUK

AF:

0.719

AC:

2667

ALSPAC

AF:

0.710

AC:

2738

ESP6500AA

AF:

0.649

AC:

2858

ESP6500EA

AF:

0.715

AC:

6148

ExAC

AF:

0.754

AC:

91471

Asia WGS

AF:

0.847

AC:

2942

AN:

3478

EpiCase

AF:

0.711

EpiControl

AF:

0.714

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.0

DANN

Benign

0.73

Eigen

Benign

0.11

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.0010

MutationTaster

Benign

1.0

P;P;P;P;P

GERP RS

2.4

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00035

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