rs11269803

Variant names:

• chr16-30992693-G-GGGGGTGGAGGA
• rs11269803
• NM_052874.5:c.*127_*128insTCCTCCACCCC

Your query was ambiguous. Multiple possible variants found:

• chr16-30992693-G-GGGGGTGGAGGA
• chr16-30992693-G-GGGGGTGGA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_052874.5(STX1B):​c.*127_*128insTCCTCCACCCC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (44481 hom., cov: 0)
  • Exomes 𝑓: 0.99 (207195 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.102
• Publications: 3 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.

• BP6: Variant 16-30992693-G-GGGGGTGGAGGA is Benign according to our data. Variant chr16-30992693-G-GGGGGTGGAGGA is described in ClinVar as Benign. ClinVar VariationId is 1291868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

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.*127_*128insTCCTCCACCCC		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.*127_*128insTCCTCCACCCC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*127_*128insTCCTCCACCCC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.960 AC: 92507 AN: 96338 Hom.: 44450 Cov.: 0

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.973

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.977

Gnomad FIN AF: 0.962

Gnomad MID AF: 0.986

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.969

GnomAD4 exome AF: 0.994 AC: 417026 AN: 419692 Hom.: 207195 Cov.: 6 AF XY: 0.994 AC XY: 218784 AN XY: 220134

African (AFR) AF: 0.940 AC: 10917 AN: 11608

American (AMR) AF: 0.993 AC: 17265 AN: 17382

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 12705 AN: 12752

East Asian (EAS) AF: 0.999 AC: 29288 AN: 29322

South Asian (SAS) AF: 0.992 AC: 40281 AN: 40606

European-Finnish (FIN) AF: 0.996 AC: 35550 AN: 35690

Middle Eastern (MID) AF: 0.996 AC: 1811 AN: 1818

European-Non Finnish (NFE) AF: 0.995 AC: 245241 AN: 246364

Other (OTH) AF: 0.992 AC: 23968 AN: 24150

GnomAD4 genome AF: 0.960 AC: 92578 AN: 96418 Hom.: 44481 Cov.: 0 AF XY: 0.962 AC XY: 43134 AN XY: 44848

African (AFR) AF: 0.907 AC: 19183 AN: 21140

American (AMR) AF: 0.973 AC: 9035 AN: 9282

Ashkenazi Jewish (ASJ) AF: 0.973 AC: 2640 AN: 2714

East Asian (EAS) AF: 0.994 AC: 3796 AN: 3818

South Asian (SAS) AF: 0.977 AC: 2844 AN: 2912

European-Finnish (FIN) AF: 0.962 AC: 4488 AN: 4664

Middle Eastern (MID) AF: 0.979 AC: 186 AN: 190

European-Non Finnish (NFE) AF: 0.975 AC: 48517 AN: 49768

Other (OTH) AF: 0.970 AC: 1232 AN: 1270

Alfa AF: 0.608 Hom.: 2185

Asia WGS AF: 0.975 AC: 3303 AN: 3386

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11269803; hg19: chr16-31004014;