16-30992649-G-GGC

Variant names:

• chr16-30992649-G-GGC
• rs201290311
• NM_052874.5:c.*171_*172insGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_052874.5(STX1B):​c.*171_*172insGC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 489,362 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (21 hom., cov: 25)
  • Exomes 𝑓: 0.0054 (13 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 16-30992649-G-GGC is Benign according to our data. Variant chr16-30992649-G-GGC is described in ClinVar as Likely_benign. ClinVar VariationId is 1200110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00916 (1068/116582) while in subpopulation AFR AF = 0.0165 (533/32332). AF 95% confidence interval is 0.0153. There are 21 homozygotes in GnomAd4. There are 480 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1068 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_*172insGC		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_*172insGC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*171_*172insGC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.00914 AC: 1065 AN: 116482 Hom.: 20 Cov.: 25

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.0421

Gnomad AMR AF: 0.00729

Gnomad ASJ AF: 0.000703

Gnomad EAS AF: 0.000293

Gnomad SAS AF: 0.00804

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.00667

Gnomad OTH AF: 0.00953

GnomAD4 exome AF: 0.00537 AC: 2002 AN: 372780 Hom.: 13 Cov.: 3 AF XY: 0.00557 AC XY: 1085 AN XY: 194944

African (AFR) AF: 0.0174 AC: 182 AN: 10472

American (AMR) AF: 0.00513 AC: 70 AN: 13658

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 32 AN: 11776

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

South Asian (SAS) AF: 0.00649 AC: 222 AN: 34196

European-Finnish (FIN) AF: 0.000806 AC: 22 AN: 27290

Middle Eastern (MID) AF: 0.0153 AC: 26 AN: 1700

European-Non Finnish (NFE) AF: 0.00583 AC: 1302 AN: 223342

Other (OTH) AF: 0.00655 AC: 146 AN: 22306

GnomAD4 genome AF: 0.00916 AC: 1068 AN: 116582 Hom.: 21 Cov.: 25 AF XY: 0.00867 AC XY: 480 AN XY: 55352

African (AFR) AF: 0.0165 AC: 533 AN: 32332

American (AMR) AF: 0.00737 AC: 75 AN: 10178

Ashkenazi Jewish (ASJ) AF: 0.000703 AC: 2 AN: 2844

East Asian (EAS) AF: 0.000294 AC: 1 AN: 3404

South Asian (SAS) AF: 0.00868 AC: 26 AN: 2996

European-Finnish (FIN) AF: 0.00108 AC: 7 AN: 6472

Middle Eastern (MID) AF: 0.0183 AC: 4 AN: 218

European-Non Finnish (NFE) AF: 0.00667 AC: 372 AN: 55744

Other (OTH) AF: 0.00883 AC: 14 AN: 1586

Alfa AF: 0.000164 Hom.: 1

ClinVar

ClinVar submissions as Germline

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
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

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;