rs191289798

Variant names:

• chr16-30992647-G-A
• rs191289798
• NM_052874.5:c.*174C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-30992647-G-A
• chr16-30992647-G-C
• chr16-30992647-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_052874.5(STX1B):​c.*174C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00171 in 517,944 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (10 hom., cov: 26)
  • Exomes 𝑓: 0.00074 (2 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.87
• Publications: 1 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: ClinGen, Orphanet
• generalized epilepsy with febrile seizures plus, type 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 16-30992647-G-A is Benign according to our data. Variant chr16-30992647-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1204794.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 611 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX1B	NM_052874.5	MANE Select	c.*174C>T		3_prime_UTR	Exon 10 of 10	NP_443106.1	P61266-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STX1B	ENST00000215095.11	TSL:1 MANE Select	c.*174C>T		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*174C>T		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.00419 AC: 610 AN: 145464 Hom.: 10 Cov.: 26

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00218

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.000166

Gnomad OTH AF: 0.00450

GnomAD4 exome AF: 0.000736 AC: 274 AN: 372380 Hom.: 2 Cov.: 2 AF XY: 0.000590 AC XY: 115 AN XY: 194822

African (AFR) AF: 0.0161 AC: 169 AN: 10470

American (AMR) AF: 0.00175 AC: 24 AN: 13686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11762

East Asian (EAS) AF: 0.0000357 AC: 1 AN: 28034

South Asian (SAS) AF: 0.0000292 AC: 1 AN: 34242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27142

Middle Eastern (MID) AF: 0.000588 AC: 1 AN: 1702

European-Non Finnish (NFE) AF: 0.000103 AC: 23 AN: 223048

Other (OTH) AF: 0.00247 AC: 55 AN: 22294

GnomAD4 genome AF: 0.00420 AC: 611 AN: 145564 Hom.: 10 Cov.: 26 AF XY: 0.00410 AC XY: 291 AN XY: 70902

African (AFR) AF: 0.0142 AC: 558 AN: 39218

American (AMR) AF: 0.00218 AC: 32 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4858

South Asian (SAS) AF: 0.00 AC: 0 AN: 4450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9544

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.000166 AC: 11 AN: 66234

Other (OTH) AF: 0.00445 AC: 9 AN: 2022

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00580

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.66
PhyloP100		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism

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: rs191289798; hg19: chr16-31003968;