rs9390459

chr6-147359223-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001127715.4(STXBP5):c.2445A>G(p.Leu815=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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]

ACMG classification

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	UniProt
STXBP5	NM_001127715.4	c.2445A>G	p.Leu815=	synonymous_variant	23/28	ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11	c.2445A>G	p.Leu815=	synonymous_variant	23/28	5	NM_001127715.4	A1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83514 AN: 151938 Hom.: 23192 Cov.: 32

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

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.: 63 AF XY: 0.555 AC XY: 403582 AN XY: 727170

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.: 32 AF XY: 0.544 AC XY: 40430 AN XY: 74324

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

Other links and lift over

dbSNP: rs9390459; hg19: chr6-147680359; COSMIC: COSV51649341;