Variant rs1156287 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178509.6(STXBP4):c.274G>A(p.Gly92Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 1,610,254 control chromosomes in the GnomAD database, including 442,597 homozygotes. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.79 ( 48226 hom., cov: 31)

Exomes 𝑓: 0.73 ( 394371 hom. )

Consequence

STXBP4
NM_178509.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98

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:

STXBP4 (HGNC:):

STXBP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.621848E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP4	NM_178509.6 linkuse as main transcript	c.274G>A	p.Gly92Arg	missense_variant	5/18	ENST00000376352.6	NP_848604.3	Q6ZWJ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STXBP4	ENST00000376352.6 linkuse as main transcript	c.274G>A	p.Gly92Arg	missense_variant	5/18	2	NM_178509.6	ENSP00000365530.2	Q6ZWJ1-1
STXBP4	ENST00000434978.6 linkuse as main transcript	c.274G>A	p.Gly92Arg	missense_variant	5/17	1		ENSP00000391087.2	E7EPP7
STXBP4	ENST00000398391.6 linkuse as main transcript	c.43G>A	p.Gly15Arg	missense_variant	4/11	1		ENSP00000381427.2	Q6ZWJ1-2
STXBP4	ENST00000405898.5 linkuse as main transcript	c.274G>A	p.Gly92Arg	missense_variant	4/11	5		ENSP00000385944.1	B5MCT9

Frequencies

GnomAD3 genomes

AF:

0.791

AC:

120191

AN:

151962

Hom.:

48165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.913

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.799

Gnomad ASJ

AF:

0.761

Gnomad EAS

AF:

0.907

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.726

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.715

Gnomad OTH

AF:

0.759

GnomAD3 exomes

AF:

0.778

AC:

193669

AN:

248784

Hom.:

76248

AF XY:

0.773

AC XY:

103845

AN XY:

134290

show subpopulations

Gnomad AFR exome

AF:

0.919

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.769

Gnomad EAS exome

AF:

0.894

Gnomad SAS exome

AF:

0.809

Gnomad FIN exome

AF:

0.726

Gnomad NFE exome

AF:

0.719

Gnomad OTH exome

AF:

0.753

GnomAD4 exome

AF:

0.733

AC:

1068277

AN:

1458176

Hom.:

394371

Cov.:

AF XY:

0.735

AC XY:

532872

AN XY:

725294

show subpopulations

Gnomad4 AFR exome

AF:

0.924

Gnomad4 AMR exome

AF:

0.855

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.928

Gnomad4 SAS exome

AF:

0.812

Gnomad4 FIN exome

AF:

0.723

Gnomad4 NFE exome

AF:

0.708

Gnomad4 OTH exome

AF:

0.744

GnomAD4 genome

AF:

0.791

AC:

120315

AN:

152078

Hom.:

48226

Cov.:

AF XY:

0.792

AC XY:

58820

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.913

Gnomad4 AMR

AF:

0.799

Gnomad4 ASJ

AF:

0.761

Gnomad4 EAS

AF:

0.908

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.726

Gnomad4 NFE

AF:

0.715

Gnomad4 OTH

AF:

0.759

Alfa

AF:

0.738

Hom.:

106136

Bravo

AF:

0.803

TwinsUK

AF:

0.722

AC:

2676

ALSPAC

AF:

0.711

AC:

2740

ESP6500AA

AF:

0.906

AC:

3992

ESP6500EA

AF:

0.717

AC:

6164

ExAC

AF:

0.780

AC:

94697

Asia WGS

AF:

0.860

AC:

2984

AN:

3472

EpiCase

AF:

0.713

EpiControl

AF:

0.718

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.8

DANN

Benign

0.15

DEOGEN2

Benign

0.0025

T;T;T;.

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.092

T;T;T;T

MetaRNN

Benign

6.6e-7

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.3

N;.;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

4.7

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.12

MutPred

0.53

Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);.;

MPC

0.18

ClinPred

0.0019

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.44

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