6-147209945-G-T

Variant summary

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

The NM_001127715.4(STXBP5):c.248+3877G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,006 control chromosomes in the GnomAD database, including 30,060 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 0.61 (30060 hom., cov: 31)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4	c.248+3877G>T		intron_variant		ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11	c.248+3877G>T		intron_variant		5	NM_001127715.4	A1

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92179 AN: 151888 Hom.: 30010 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.607 AC: 92284 AN: 152006 Hom.: 30060 Cov.: 31 AF XY: 0.607 AC XY: 45070 AN XY: 74298

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.588

Alfa AF: 0.466 Hom.: 2708

Bravo AF: 0.615

Asia WGS AF: 0.605 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.4
Dann	Benign	0.57

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: rs2786189; hg19: chr6-147531081;