rs17855121

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_052874.5(STX1B):c.840A>G(p.Ser280Ser) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.606

Publications

18 publications found

Variant links:

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]

STX1B Gene-Disease associations (from GenCC):

generalized epilepsy with febrile seizures plus
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
generalized epilepsy with febrile seizures plus, type 9
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

STX1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
STX1B	NM_052874.5 link	c.840A>G	p.Ser280Ser	synonymous_variant	Exon 10 of 10	ENST00000215095.11	NP_443106.1
STX1B	XM_017022893.2 link	c.822A>G	p.Ser274Ser	synonymous_variant	Exon 10 of 10		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11 link	c.840A>G	p.Ser280Ser	synonymous_variant	Exon 10 of 10	1	NM_052874.5	ENSP00000215095.5
STX1B	ENST00000565419.2 link	c.*234A>G		downstream_gene_variant		2		ENSP00000455899.1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36525

AN:

151312

Hom.:

5079

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.248

AC:

61829

AN:

249690

AF XY:

0.245

show subpopulations

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 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.:

AF XY:

0.281

AC XY:

204105

AN XY:

726486

show subpopulations

African (AFR)

AF:

0.134

AC:

4499

AN:

33456

American (AMR)

AF:

0.318

AC:

14216

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5358

AN:

26104

East Asian (EAS)

AF:

0.000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.156

AC:

13469

AN:

86222

European-Finnish (FIN)

AF:

0.314

AC:

16717

AN:

53286

Middle Eastern (MID)

AF:

0.148

AC:

852

AN:

5766

European-Non Finnish (NFE)

AF:

0.310

AC:

344222

AN:

1110750

Other (OTH)

AF:

0.260

AC:

15659

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

13240

26480

39720

52960

66200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10960

21920

32880

43840

54800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.241

AC:

36539

AN:

151428

Hom.:

5082

Cov.:

AF XY:

0.239

AC XY:

17658

AN XY:

73956

show subpopulations

African (AFR)

AF:

0.141

AC:

5834

AN:

41280

American (AMR)

AF:

0.300

AC:

4551

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

717

AN:

3468

East Asian (EAS)

AF:

0.00330

AC:

AN:

5148

South Asian (SAS)

AF:

0.136

AC:

654

AN:

4814

European-Finnish (FIN)

AF:

0.303

AC:

3158

AN:

10414

Middle Eastern (MID)

AF:

0.137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.309

AC:

20977

AN:

67836

Other (OTH)

AF:

0.220

AC:

462

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1290

2581

3871

5162

6452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.260

Hom.:

4034

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Generalized epilepsy with febrile seizures plus, type 9

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 54% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 50. Only high quality variants are reported. -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

DANN

Benign

0.75

PhyloP100

0.61

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over