rs17855121

chr16-30992848-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_052874.5(STX1B):c.840A>G(p.Ser280=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,611,714 control chromosomes in the GnomAD database, including 68,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5082 hom., cov: 30)
  • Exomes 𝑓: 0.28 (63097 hom.)
• Consequence: STX1B NM_052874.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.606

Genes affected

STX1B (HGNC:18539): (syntaxin 1B) The protein encoded by this gene belongs to a family of proteins thought to play a role in the exocytosis of synaptic vesicles. Vesicle exocytosis releases vesicular contents and is important to various cellular functions. For instance, the secretion of transmitters from neurons plays an important role in synaptic transmission. After exocytosis, the membrane and proteins from the vesicle are retrieved from the plasma membrane through the process of endocytosis. Mutations in this gene have been identified as one cause of fever-associated epilepsy syndromes. A possible link between this gene and Parkinson's disease has also been suggested. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 16-30992848-T-C is Benign according to our data. Variant chr16-30992848-T-C is described in ClinVar as [Benign]. Clinvar id is 586687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.606 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1B	NM_052874.5	c.840A>G	p.Ser280=	synonymous_variant	10/10	ENST00000215095.11
STX1B	XM_017022893.2	c.822A>G	p.Ser274=	synonymous_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1B	ENST00000215095.11	c.840A>G	p.Ser280=	synonymous_variant	10/10	1	NM_052874.5	P1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36525 AN: 151312 Hom.: 5079 Cov.: 30

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.00329

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.221

GnomAD3 exomes AF: 0.248 AC: 61829 AN: 249690 Hom.: 8890 AF XY: 0.245 AC XY: 33190 AN XY: 135226

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.326

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.000980

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.316

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.284 AC: 415022 AN: 1460286 Hom.: 63097 Cov.: 36 AF XY: 0.281 AC XY: 204105 AN XY: 726486

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.000756

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.310

Gnomad4 OTH exome AF: 0.260

GnomAD4 genome AF: 0.241 AC: 36539 AN: 151428 Hom.: 5082 Cov.: 30 AF XY: 0.239 AC XY: 17658 AN XY: 73956

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.00330

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.220

Alfa AF: 0.279 Hom.: 3748

Bravo AF: 0.235

Asia WGS AF: 0.0870 AC: 303 AN: 3478

EpiCase AF: 0.294

EpiControl AF: 0.277

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2018	- -

Generalized epilepsy with febrile seizures plus, type 9 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	8.3
Dann	Benign	0.75

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: rs17855121; hg19: chr16-31004169; COSMIC: COSV52679654; COSMIC: COSV52679654;