rs4717806

chr7-73702147-T-Achr7-73702147-T-Cchr7-73702147-T-G

Variant summary

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

The NM_004603.4(STX1A):c.678+698A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,014 control chromosomes in the GnomAD database, including 6,253 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 0.26 (6253 hom., cov: 31)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

Genes affected

STX1A (HGNC:11433): (syntaxin 1A) This gene encodes a member of the syntaxin superfamily. Syntaxins are nervous system-specific proteins implicated in the docking of synaptic vesicles with the presynaptic plasma membrane. Syntaxins possess a single C-terminal transmembrane domain, a SNARE [Soluble NSF (N-ethylmaleimide-sensitive fusion protein)-Attachment protein REceptor] domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage dependent calcium and potassium channels via the C-terminal H3 domain. This gene product is a key molecule in ion channel regulation and synaptic exocytosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1A	NM_004603.4	c.678+698A>T		intron_variant		ENST00000222812.8
STX1A	NM_001165903.2	c.678+698A>T		intron_variant
STX1A	XM_047420777.1	c.793+583A>T		intron_variant
STX1A	XM_047420778.1	c.678+698A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1A	ENST00000222812.8	c.678+698A>T		intron_variant		1	NM_004603.4	P1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39523 AN: 151896 Hom.: 6257 Cov.: 31

Gnomad AFR AF: 0.0764

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.260 AC: 39521 AN: 152014 Hom.: 6253 Cov.: 31 AF XY: 0.264 AC XY: 19626 AN XY: 74276

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.267

Alfa AF: 0.298 Hom.: 932

Bravo AF: 0.240

Asia WGS AF: 0.263 AC: 916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.9
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4717806; hg19: chr7-73116477;