chr16-30993491-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052874.5(STX1B):c.538-7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 1,612,364 control chromosomes in the GnomAD database, including 123,874 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11173 hom., cov: 32)

Exomes 𝑓: 0.38 ( 112701 hom. )

Consequence

STX1B
NM_052874.5 splice_region, intron

Scores

Splicing: ADA: 0.00004004

Clinical Significance

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

Conservation

PhyloP100: -6.07

Publications

72 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-30993491-T-C is Benign according to our data. Variant chr16-30993491-T-C is described in ClinVar as Benign. ClinVar VariationId is 586685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1B	NM_052874.5 link	c.538-7A>G		splice_region_variant, intron_variant	Intron 7 of 9	ENST00000215095.11	NP_443106.1	P61266-1
STX1B	XM_017022893.2 link	c.520-7A>G		splice_region_variant, intron_variant	Intron 7 of 9		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11 link	c.538-7A>G		splice_region_variant, intron_variant	Intron 7 of 9	1	NM_052874.5	ENSP00000215095.5		P61266-1
STX1B	ENST00000565419.2 link	c.538-7A>G		splice_region_variant, intron_variant	Intron 7 of 8	2		ENSP00000455899.1		P61266-2

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

56918

AN:

151916

Hom.:

11162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.319

Gnomad EAS

AF:

0.0994

Gnomad SAS

AF:

0.695

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.344

GnomAD2 exomes

AF:

0.392

AC:

98069

AN:

250472

AF XY:

0.405

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.342

Gnomad EAS exome

AF:

0.0934

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.365

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.382

AC:

557411

AN:

1460330

Hom.:

112701

Cov.:

AF XY:

0.389

AC XY:

282847

AN XY:

726434

show subpopulations

African (AFR)

AF:

0.382

AC:

12795

AN:

33474

American (AMR)

AF:

0.412

AC:

18415

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8938

AN:

26132

East Asian (EAS)

AF:

0.0866

AC:

3436

AN:

39698

South Asian (SAS)

AF:

0.670

AC:

57741

AN:

86240

European-Finnish (FIN)

AF:

0.367

AC:

19273

AN:

52538

Middle Eastern (MID)

AF:

0.288

AC:

1664

AN:

5768

European-Non Finnish (NFE)

AF:

0.371

AC:

412848

AN:

1111414

Other (OTH)

AF:

0.369

AC:

22301

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16552

33104

49655

66207

82759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13142

26284

39426

52568

65710

<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:

0.375

AC:

56951

AN:

152034

Hom.:

11173

Cov.:

AF XY:

0.376

AC XY:

27978

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.380

AC:

15772

AN:

41462

American (AMR)

AF:

0.383

AC:

5857

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

1107

AN:

3468

East Asian (EAS)

AF:

0.0990

AC:

512

AN:

5170

South Asian (SAS)

AF:

0.694

AC:

3343

AN:

4820

European-Finnish (FIN)

AF:

0.354

AC:

3747

AN:

10570

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25491

AN:

67958

Other (OTH)

AF:

0.350

AC:

737

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1818

3636

5455

7273

9091

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

566

1132

1698

2264

2830

<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:

0.369

Hom.:

19156

Bravo

AF:

0.366

Asia WGS

AF:

0.439

AC:

1524

AN:

3478

EpiCase

AF:

0.364

EpiControl

AF:

0.353

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Generalized epilepsy with febrile seizures plus, type 9

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 58% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 54. Only high quality variants are reported. -

Inborn genetic diseases

Benign:1

May 31, 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

-0.86

CADD

Benign

0.015

(source)

DANN

Benign

0.57

PhyloP100

-6.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000040

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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