16-30992649-G-GGC

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High AC in GnomAd at 1065 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1B	NM_052874.5	c.*171_*172insGC		3_prime_UTR_variant	10/10	ENST00000215095.11
STX1B	XM_017022893.2	c.*171_*172insGC		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1B	ENST00000215095.11	c.*171_*172insGC		3_prime_UTR_variant	10/10	1	NM_052874.5	P1

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

Gnomad4 AFR exome AF: 0.0174

Gnomad4 AMR exome AF: 0.00513

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00649

Gnomad4 FIN exome AF: 0.000806

Gnomad4 NFE exome AF: 0.00583

Gnomad4 OTH exome AF: 0.00655

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

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.00737

Gnomad4 ASJ AF: 0.000703

Gnomad4 EAS AF: 0.000294

Gnomad4 SAS AF: 0.00868

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.00667

Gnomad4 OTH AF: 0.00883

Alfa AF: 0.000164 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201290311; hg19: chr16-31003970;