chr6-147228161-A-G

Variant names:

• chr6-147228161-A-G
• rs556493
• NM_001127715.4:c.249-7089A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127715.4(STXBP5):​c.249-7089A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,700 control chromosomes in the GnomAD database, including 23,800 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 0.55 (23800 hom., cov: 31)
• Consequence: STXBP5 NM_001127715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853
• Publications: 6 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]

ENSG00000293909 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	NM_001127715.4	MANE Select	c.249-7089A>G		intron	N/A	NP_001121187.1
	STXBP5	NM_001394409.1		c.249-7089A>G		intron	N/A	NP_001381338.1
	STXBP5	NM_139244.6		c.249-7089A>G		intron	N/A	NP_640337.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STXBP5	ENST00000321680.11	TSL:5 MANE Select	c.249-7089A>G		intron	N/A	ENSP00000321826.6
	STXBP5	ENST00000367481.7	TSL:1	c.249-7089A>G		intron	N/A	ENSP00000356451.3
	STXBP5	ENST00000546097.5	TSL:1	c.357-7089A>G		intron	N/A	ENSP00000441479.2

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83227 AN: 151582 Hom.: 23771 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.549 AC: 83313 AN: 151700 Hom.: 23800 Cov.: 31 AF XY: 0.551 AC XY: 40821 AN XY: 74110

African (AFR) AF: 0.712 AC: 29502 AN: 41434

American (AMR) AF: 0.456 AC: 6925 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1671 AN: 3466

East Asian (EAS) AF: 0.711 AC: 3667 AN: 5154

South Asian (SAS) AF: 0.553 AC: 2659 AN: 4812

European-Finnish (FIN) AF: 0.504 AC: 5298 AN: 10514

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31826 AN: 67830

Other (OTH) AF: 0.541 AC: 1140 AN: 2106

Alfa AF: 0.381 Hom.: 1169

Bravo AF: 0.551

Asia WGS AF: 0.603 AC: 2099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs556493; hg19: chr6-147549297;