chr6-147379997-T-G

Position:

• chr6-147379997-T-G

Variant summary

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

The NM_001127715.4(STXBP5):​c.3194-2781T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,756 control chromosomes in the GnomAD database, including 29,545 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 0.62 (29545 hom., cov: 30)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STXBP5	NM_001127715.4	c.3194-2781T>G		intron_variant		ENST00000321680.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STXBP5	ENST00000321680.11	c.3194-2781T>G		intron_variant		5	NM_001127715.4	A1

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94044 AN: 151638 Hom.: 29541 Cov.: 30

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.460

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.610

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

GnomAD4 genome AF: 0.620 AC: 94094 AN: 151756 Hom.: 29545 Cov.: 30 AF XY: 0.616 AC XY: 45685 AN XY: 74146

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.606

Alfa AF: 0.592 Hom.: 34396

Bravo AF: 0.634

Asia WGS AF: 0.599 AC: 2075 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.88
DANN	Benign	0.50

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: rs9373523; hg19: chr6-147701133;