rs941298

Variant names:

• chr7-73710933-G-A
• rs941298
• NM_004603.4:c.31-1811C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-73710933-G-A
• chr7-73710933-G-C
• chr7-73710933-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.91).
• 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 rank	MANE	Protein	UniProt
STX1A	NM_004603.4	c.31-1811C>T		intron_variant	Intron 1 of 9	ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.31-1811C>T		intron_variant	Intron 1 of 9		NP_001159375.1
STX1A	XM_047420777.1	c.31-1811C>T		intron_variant	Intron 1 of 8		XP_047276733.1
STX1A	XM_047420778.1	c.31-1811C>T		intron_variant	Intron 1 of 8		XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.31-1811C>T		intron_variant	Intron 1 of 9	1	NM_004603.4	ENSP00000222812.3

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

African (AFR) AF: 0.129 AC: 5357 AN: 41536

American (AMR) AF: 0.316 AC: 4826 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 865 AN: 3468

East Asian (EAS) AF: 0.157 AC: 810 AN: 5164

South Asian (SAS) AF: 0.362 AC: 1742 AN: 4814

European-Finnish (FIN) AF: 0.417 AC: 4404 AN: 10558

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

European-Non Finnish (NFE) AF: 0.342 AC: 23248 AN: 67962

Other (OTH) AF: 0.272 AC: 573 AN: 2108

Alfa AF: 0.299 Hom.: 1220

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
PhyloP100		-0.029
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: rs941298; hg19: chr7-73125263;