6-147209945-G-T

Variant names:

• chr6-147209945-G-T
• rs2786189
• NM_001127715.4:c.248+3877G>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.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
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 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.248+3877G>T		intron	N/A	NP_001121187.1	Q5T5C0-1
	STXBP5	NM_001394409.1		c.248+3877G>T		intron	N/A	NP_001381338.1	H0Y332
	STXBP5	NM_139244.6		c.248+3877G>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.248+3877G>T		intron	N/A	ENSP00000321826.6	Q5T5C0-1
	STXBP5	ENST00000367481.7	TSL:1	c.248+3877G>T		intron	N/A	ENSP00000356451.3	Q5T5C0-2
	STXBP5	ENST00000546097.5	TSL:1	c.356+3877G>T		intron	N/A	ENSP00000441479.2	F6VFW0

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

African (AFR) AF: 0.857 AC: 35574 AN: 41494

American (AMR) AF: 0.490 AC: 7490 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1826 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3715 AN: 5170

South Asian (SAS) AF: 0.555 AC: 2671 AN: 4814

European-Finnish (FIN) AF: 0.519 AC: 5466 AN: 10540

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

European-Non Finnish (NFE) AF: 0.496 AC: 33671 AN: 67942

Other (OTH) AF: 0.588 AC: 1238 AN: 2104

Alfa AF: 0.519 Hom.: 6926

Bravo AF: 0.615

Asia WGS AF: 0.605 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.57
PhyloP100		-0.021
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: rs2786189; hg19: chr6-147531081;