rs4889606

Variant names:

• chr16-30999862-A-G
• rs4889606
• NM_052874.5:c.280+1066T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052874.5(STX1B):​c.280+1066T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,030 control chromosomes in the GnomAD database, including 10,925 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 0.35 (10925 hom., cov: 32)
• Consequence: STX1B NM_052874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.240
• Publications: 45 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STX1B	NM_052874.5	c.280+1066T>C		intron_variant	Intron 4 of 9	ENST00000215095.11	NP_443106.1
STX1B	XM_017022893.2	c.262+1066T>C		intron_variant	Intron 4 of 9		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11	c.280+1066T>C		intron_variant	Intron 4 of 9	1	NM_052874.5	ENSP00000215095.5
STX1B	ENST00000565419.2	c.280+1066T>C		intron_variant	Intron 4 of 8	2		ENSP00000455899.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53765 AN: 151912 Hom.: 10917 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.890

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.406

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.354 AC: 53797 AN: 152030 Hom.: 10925 Cov.: 32 AF XY: 0.356 AC XY: 26478 AN XY: 74320

African (AFR) AF: 0.217 AC: 9015 AN: 41476

American (AMR) AF: 0.405 AC: 6185 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1742 AN: 3468

East Asian (EAS) AF: 0.890 AC: 4608 AN: 5176

South Asian (SAS) AF: 0.190 AC: 917 AN: 4816

European-Finnish (FIN) AF: 0.393 AC: 4152 AN: 10560

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25764 AN: 67942

Other (OTH) AF: 0.404 AC: 851 AN: 2106

Alfa AF: 0.386 Hom.: 19306

Bravo AF: 0.363

Asia WGS AF: 0.467 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.14
DANN	Benign	0.74
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4889606; hg19: chr16-31011183;