16-30992550-G-A

Position:

• chr16-30992550-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_052874.5(STX1B):​c.*271C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00364 in 432,236 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (4 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.958

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 16-30992550-G-A is Benign according to our data. Variant chr16-30992550-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1216622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00645 (979/151882) while in subpopulation AFR AF= 0.0185 (766/41362). AF 95% confidence interval is 0.0174. There are 5 homozygotes in gnomad4. There are 470 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 979 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STX1B	NM_052874.5	c.*271C>T		3_prime_UTR_variant	10/10	ENST00000215095.11	NP_443106.1
STX1B	XM_017022893.2	c.*271C>T		3_prime_UTR_variant	10/10		XP_016878382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STX1B	ENST00000215095.11	c.*271C>T		3_prime_UTR_variant	10/10	1	NM_052874.5	ENSP00000215095	P1

Frequencies

GnomAD3 genomes AF: 0.00643 AC: 976 AN: 151764 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.0185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00212 AC: 594 AN: 280354 Hom.: 4 Cov.: 0 AF XY: 0.00216 AC XY: 314 AN XY: 145468

Gnomad4 AFR exome AF: 0.0195

Gnomad4 AMR exome AF: 0.00259

Gnomad4 ASJ exome AF: 0.0294

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000148

Gnomad4 FIN exome AF: 0.0000534

Gnomad4 NFE exome AF: 0.000351

Gnomad4 OTH exome AF: 0.00376

GnomAD4 genome AF: 0.00645 AC: 979 AN: 151882 Hom.: 5 Cov.: 31 AF XY: 0.00633 AC XY: 470 AN XY: 74238

Gnomad4 AFR AF: 0.0185

Gnomad4 AMR AF: 0.00328

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00523 Hom.: 1

Bravo AF: 0.00725

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.4
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs138046858; hg19: chr16-31003871;