rs12445568

Positions:

chr16-30993491-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
STX1B	NM_052874.5 linkuse as main transcript	c.538-7A>G		splice_region_variant, intron_variant		ENST00000215095.11	NP_443106.1	P61266-1
STX1B	XM_017022893.2 linkuse as main transcript	c.520-7A>G		splice_region_variant, intron_variant			XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11 linkuse as main transcript	c.538-7A>G		splice_region_variant, intron_variant		1	NM_052874.5	ENSP00000215095.5		P61266-1
STX1B	ENST00000565419.2 linkuse as main transcript	c.538-7A>G		splice_region_variant, intron_variant		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

GnomAD3 exomes

AF:

0.392

AC:

98069

AN:

250472

Hom.:

21563

AF XY:

0.405

AC XY:

54820

AN XY:

135412

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 SAS exome

AF:

0.678

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

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.0866

Gnomad4 SAS exome

AF:

0.670

Gnomad4 FIN exome

AF:

0.367

Gnomad4 NFE exome

AF:

0.371

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.375

AC:

56951

AN:

152034

Hom.:

11173

Cov.:

AF XY:

0.376

AC XY:

27978

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.319

Gnomad4 EAS

AF:

0.0990

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.372

Hom.:

14972

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Generalized epilepsy with febrile seizures plus, type 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 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

-0.86

CADD

Benign

0.015

DANN

Benign

0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over