rs1039085

Positions:

• chr6-147314411-C-T

Variant summary

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

The NM_001127715.4(STXBP5):​c.1361+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,392,420 control chromosomes in the GnomAD database, including 232,782 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 0.57 (24777 hom., cov: 31)
  • Exomes 𝑓: 0.58 (208005 hom.)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4	c.1361+80C>T		intron_variant		ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11	c.1361+80C>T		intron_variant		5	NM_001127715.4	A1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86227 AN: 151778 Hom.: 24777 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.576 AC: 714607 AN: 1240524 Hom.: 208005 Cov.: 17 AF XY: 0.576 AC XY: 360717 AN XY: 626762

Gnomad4 AFR exome AF: 0.556

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.554

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.541

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.562

GnomAD4 genome AF: 0.568 AC: 86275 AN: 151896 Hom.: 24777 Cov.: 31 AF XY: 0.563 AC XY: 41757 AN XY: 74222

Gnomad4 AFR AF: 0.564

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.535

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.554

Alfa AF: 0.588 Hom.: 25722

Bravo AF: 0.572

Asia WGS AF: 0.452 AC: 1570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.20
DANN	Benign	0.32

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: rs1039085; hg19: chr6-147635547;