rs201290311

Variant names:

• chr16-30992649-G-GGA
• rs201290311
• NM_052874.5:c.*171_*172insTC

Your query was ambiguous. Multiple possible variants found:

• chr16-30992649-G-GGA
• chr16-30992649-G-GGC
• chr16-30992649-G-GGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_052874.5(STX1B):​c.*171_*172insTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 489,304 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000086 (0 hom., cov: 25)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.16
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 12 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.*171_*172insTC		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.*171_*172insTC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*171_*172insTC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.00000858 AC: 1 AN: 116504 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000179

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000322 AC: 12 AN: 372800 Hom.: 0 Cov.: 3 AF XY: 0.0000564 AC XY: 11 AN XY: 194952

African (AFR) AF: 0.00 AC: 0 AN: 10472

American (AMR) AF: 0.00 AC: 0 AN: 13664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11776

East Asian (EAS) AF: 0.00 AC: 0 AN: 28040

South Asian (SAS) AF: 0.000205 AC: 7 AN: 34196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1702

European-Non Finnish (NFE) AF: 0.0000224 AC: 5 AN: 223354

Other (OTH) AF: 0.00 AC: 0 AN: 22306

GnomAD4 genome AF: 0.00000858 AC: 1 AN: 116504 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 55288

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32262

American (AMR) AF: 0.00 AC: 0 AN: 10158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2844

East Asian (EAS) AF: 0.00 AC: 0 AN: 3410

South Asian (SAS) AF: 0.00 AC: 0 AN: 2986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000179 AC: 1 AN: 55750

Other (OTH) AF: 0.00 AC: 0 AN: 1574

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

Splicing

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

Other links and lift over

dbSNP: rs201290311; hg19: chr16-31003970;