6-147349465-A-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127715.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	NM_001127715.4	MANE Select	c.2255-3858A>T		intron	N/A	NP_001121187.1	Q5T5C0-1
	STXBP5	NM_001394409.1		c.2207-3858A>T		intron	N/A	NP_001381338.1	H0Y332
	STXBP5	NM_139244.6		c.2147-3858A>T		intron	N/A	NP_640337.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	ENST00000321680.11	TSL:5 MANE Select	c.2255-3858A>T		intron	N/A	ENSP00000321826.6	Q5T5C0-1
	STXBP5	ENST00000367481.7	TSL:1	c.2147-3858A>T		intron	N/A	ENSP00000356451.3	Q5T5C0-2
	STXBP5	ENST00000964473.1		c.2210-3858A>T		intron	N/A	ENSP00000634532.1

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

African (AFR) AF: 0.270 AC: 11225 AN: 41500

American (AMR) AF: 0.498 AC: 7588 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1363 AN: 5176

South Asian (SAS) AF: 0.444 AC: 2138 AN: 4812

European-Finnish (FIN) AF: 0.475 AC: 5010 AN: 10552

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35598 AN: 67944

Other (OTH) AF: 0.449 AC: 948 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12199542; hg19: chr6-147670601;