rs941298

chr7-73710933-G-A

Variant summary

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

The NM_004603.4(STX1A):c.31-1811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,094 control chromosomes in the GnomAD database, including 6,560 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 0.28 (6560 hom., cov: 32)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1A	NM_004603.4	c.31-1811C>T		intron_variant		ENST00000222812.8
STX1A	NM_001165903.2	c.31-1811C>T		intron_variant
STX1A	XM_047420777.1	c.31-1811C>T		intron_variant
STX1A	XM_047420778.1	c.31-1811C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1A	ENST00000222812.8	c.31-1811C>T		intron_variant		1	NM_004603.4	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42103 AN: 151976 Hom.: 6563 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.277 AC: 42117 AN: 152094 Hom.: 6560 Cov.: 32 AF XY: 0.280 AC XY: 20832 AN XY: 74330

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.362

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.272

Alfa AF: 0.305 Hom.: 1217

Bravo AF: 0.259

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.58

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: rs941298; hg19: chr7-73125263;