rs4363087

Positions:

• chr7-73703866-T-C

Variant summary

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

The NM_004603.4(STX1A):​c.467-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 1,599,828 control chromosomes in the GnomAD database, including 132,502 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 0.33 (10005 hom., cov: 32)
  • Exomes 𝑓: 0.40 (122497 hom.)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

LOC105375350 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1A	NM_004603.4	c.467-38A>G		intron_variant		ENST00000222812.8
LOC105375350	XR_927656.3	n.436+341T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1A	ENST00000222812.8	c.467-38A>G		intron_variant		1	NM_004603.4	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50385 AN: 151924 Hom.: 10007 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.336

GnomAD3 exomes AF: 0.421 AC: 99554 AN: 236522 Hom.: 22501 AF XY: 0.426 AC XY: 54469 AN XY: 127954

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.505

Gnomad ASJ exome AF: 0.293

Gnomad EAS exome AF: 0.588

Gnomad SAS exome AF: 0.530

Gnomad FIN exome AF: 0.460

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.404 AC: 584194 AN: 1447786 Hom.: 122497 Cov.: 33 AF XY: 0.407 AC XY: 292734 AN XY: 719628

Gnomad4 AFR exome AF: 0.0932

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.522

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.379

GnomAD4 genome AF: 0.331 AC: 50389 AN: 152042 Hom.: 10005 Cov.: 32 AF XY: 0.340 AC XY: 25292 AN XY: 74294

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.339

Alfa AF: 0.350 Hom.: 1920

Bravo AF: 0.316

Asia WGS AF: 0.554 AC: 1925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4363087; hg19: chr7-73118196; COSMIC: COSV56108886; COSMIC: COSV56108886;