Variant 6-147359223-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001127715.4(STXBP5):c.2445A>G(p.Leu815Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,613,772 control chromosomes in the GnomAD database, including 251,496 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 23202 hom., cov: 32)

Exomes 𝑓: 0.56 ( 228294 hom. )

Consequence

STXBP5
NM_001127715.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0930

Variant links:

Genes affected

STXBP5 (HGNC:19665): (syntaxin binding protein 5) Syntaxin 1 is a component of the 7S and 20S SNARE complexes which are involved in docking and fusion of synaptic vesicles with the presynaptic plasma membrane. This gene encodes a syntaxin 1 binding protein. In rat, a similar protein dissociates syntaxin 1 from the Munc18/n-Sec1/rbSec1 complex to form a 10S complex, an intermediate which can be converted to the 7S SNARE complex. Thus this protein is thought to be involved in neurotransmitter release by stimulating SNARE complex formation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

STXBP5 links:

STXBP5 (HGNC:):

STXBP5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STXBP5	NM_001127715.4 linkuse as main transcript	c.2445A>G	p.Leu815Leu	synonymous_variant	23/28	ENST00000321680.11	NP_001121187.1	Q5T5C0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STXBP5	ENST00000321680.11 linkuse as main transcript	c.2445A>G	p.Leu815Leu	synonymous_variant	23/28	5	NM_001127715.4	ENSP00000321826.6		Q5T5C0-1

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83514

AN:

151938

Hom.:

23192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.580

Gnomad AMI

AF:

0.487

Gnomad AMR

AF:

0.559

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.525

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.530

AC:

133264

AN:

251250

Hom.:

36179

AF XY:

0.531

AC XY:

72082

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.570

Gnomad AMR exome

AF:

0.556

Gnomad ASJ exome

AF:

0.554

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.530

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.561

Gnomad OTH exome

AF:

0.538

GnomAD4 exome

AF:

0.556

AC:

813023

AN:

1461716

Hom.:

228294

Cov.:

AF XY:

0.555

AC XY:

403582

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.582

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.511

Gnomad4 NFE exome

AF:

0.570

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.550

AC:

83566

AN:

152056

Hom.:

23202

Cov.:

AF XY:

0.544

AC XY:

40430

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.580

Gnomad4 AMR

AF:

0.560

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.524

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.555

Alfa

AF:

0.557

Hom.:

58264

Bravo

AF:

0.555

Asia WGS

AF:

0.432

AC:

1501

AN:

3478

EpiCase

AF:

0.567

EpiControl

AF:

0.574

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

DANN

Benign

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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