rs11973069

Positions:

• chr7-73711334-C-T

Variant summary

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

The NM_004603.4(STX1A):​c.31-2212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0296 in 153,110 control chromosomes in the GnomAD database, including 215 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 0.030 (215 hom., cov: 31)
  • Exomes 𝑓: 0.012 (0 hom.)
• Consequence: STX1A NM_004603.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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]

MIR4284 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1A	NM_004603.4	c.31-2212G>A		intron_variant		ENST00000222812.8	NP_004594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1A	ENST00000222812.8	c.31-2212G>A		intron_variant		1	NM_004603.4	ENSP00000222812.3

Frequencies

GnomAD3 genomes AF: 0.0297 AC: 4509 AN: 152020 Hom.: 215 Cov.: 31

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00610 AC: 40 AN: 6556 Hom.: 0 AF XY: 0.00157 AC XY: 5 AN XY: 3176

Gnomad AFR exome AF: 0.0904

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00490

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00649

GnomAD4 exome AF: 0.0123 AC: 12 AN: 972 Hom.: 0 Cov.: 0 AF XY: 0.0116 AC XY: 6 AN XY: 518

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0750

GnomAD4 genome AF: 0.0297 AC: 4519 AN: 152138 Hom.: 215 Cov.: 31 AF XY: 0.0283 AC XY: 2106 AN XY: 74382

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.0228 Hom.: 14

Bravo AF: 0.0339

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.54

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: rs11973069; hg19: chr7-73125664;