6-147349465-A-T

Variant names:

• chr6-147349465-A-T
• rs12199542
• NM_001127715.4:c.2255-3858A>T

Variant summary

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

The NM_001127715.4(STXBP5):​c.2255-3858A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,010 control chromosomes in the GnomAD database, including 15,413 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 0.44 (15413 hom., cov: 32)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STXBP5	NM_001127715.4	c.2255-3858A>T		intron_variant	Intron 21 of 27	ENST00000321680.11	NP_001121187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STXBP5	ENST00000321680.11	c.2255-3858A>T		intron_variant	Intron 21 of 27	5	NM_001127715.4	ENSP00000321826.6

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66182 AN: 151892 Hom.: 15406 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.436 AC: 66204 AN: 152010 Hom.: 15413 Cov.: 32 AF XY: 0.433 AC XY: 32136 AN XY: 74290

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.444

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.449

Alfa AF: 0.338 Hom.: 954

Bravo AF: 0.431

Asia WGS AF: 0.375 AC: 1302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.66

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: rs12199542; hg19: chr6-147670601;