rs4717806

Variant names:

• chr7-73702147-T-A
• rs4717806
• NM_004603.4:c.678+698A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-73702147-T-A
• chr7-73702147-T-C
• chr7-73702147-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

STX1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004603.4. 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
	STX1A	NM_004603.4	MANE Select	c.678+698A>T		intron	N/A	NP_004594.1
	STX1A	NM_001165903.2		c.678+698A>T		intron	N/A	NP_001159375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX1A	ENST00000222812.8	TSL:1 MANE Select	c.678+698A>T		intron	N/A	ENSP00000222812.3
	STX1A	ENST00000395156.7	TSL:1	c.678+698A>T		intron	N/A	ENSP00000378585.3
	STX1A	ENST00000395154.7	TSL:3	c.793+583A>T		intron	N/A	ENSP00000378583.3

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

African (AFR) AF: 0.0761 AC: 3161 AN: 41520

American (AMR) AF: 0.306 AC: 4670 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 831 AN: 3468

East Asian (EAS) AF: 0.150 AC: 777 AN: 5168

South Asian (SAS) AF: 0.343 AC: 1648 AN: 4798

European-Finnish (FIN) AF: 0.420 AC: 4424 AN: 10538

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23157 AN: 67942

Other (OTH) AF: 0.267 AC: 562 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.80
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs4717806; hg19: chr7-73116477;