rs6951030

Positions:

• chr7-73718911-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.30+691A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 151,268 control chromosomes in the GnomAD database, including 3,598 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 0.21 (3598 hom., cov: 31)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1A	NM_004603.4	c.30+691A>C		intron_variant		ENST00000222812.8	NP_004594.1
STX1A	NM_001165903.2	c.30+691A>C		intron_variant			NP_001159375.1
STX1A	XM_047420777.1	c.30+691A>C		intron_variant			XP_047276733.1
STX1A	XM_047420778.1	c.30+691A>C		intron_variant			XP_047276734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.30+691A>C		intron_variant		1	NM_004603.4	ENSP00000222812.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31194 AN: 151152 Hom.: 3591 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.207 AC: 31237 AN: 151268 Hom.: 3598 Cov.: 31 AF XY: 0.202 AC XY: 14907 AN XY: 73872

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0439

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.211

Alfa AF: 0.183 Hom.: 3378

Bravo AF: 0.209

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.66

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: rs6951030; hg19: chr7-73133241;