rs659399

chr6-147294574-G-Achr6-147294574-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127715.4(STXBP5):c.917+3402G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,594 control chromosomes in the GnomAD database, including 17,793 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 0.48 (17793 hom., cov: 31)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4	c.917+3402G>A		intron_variant		ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11	c.917+3402G>A		intron_variant		5	NM_001127715.4	A1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73081 AN: 151480 Hom.: 17774 Cov.: 31

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.477

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.483 AC: 73149 AN: 151594 Hom.: 17793 Cov.: 31 AF XY: 0.488 AC XY: 36088 AN XY: 74026

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.480

Alfa AF: 0.468 Hom.: 7119

Bravo AF: 0.478

Asia WGS AF: 0.578 AC: 2012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.99
Dann	Benign	0.37

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: rs659399; hg19: chr6-147615710;