chr16-30992641-C-CG

Variant names:

• chr16-30992641-C-CG
• rs56353515
• NM_052874.5:c.*179dupC

Variant summary

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

The NM_052874.5(STX1B):​c.*179dupC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (243 hom., cov: 0)
  • Exomes 𝑓: 0.040 (6 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.551
• 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 16-30992641-C-CG is Benign according to our data. Variant chr16-30992641-C-CG is described in ClinVar as Benign. ClinVar VariationId is 1267591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 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.*179dupC		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.*179dupC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*179dupC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 3790 AN: 100238 Hom.: 240 Cov.: 0

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0129

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00193

Gnomad FIN AF: 0.00407

Gnomad MID AF: 0.00510

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.0265

GnomAD4 exome AF: 0.0397 AC: 12008 AN: 302400 Hom.: 6 Cov.: 0 AF XY: 0.0387 AC XY: 6091 AN XY: 157352

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

African (AFR) AF: 0.165 AC: 1500 AN: 9114

American (AMR) AF: 0.0370 AC: 405 AN: 10952

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 421 AN: 9920

East Asian (EAS) AF: 0.000610 AC: 14 AN: 22968

South Asian (SAS) AF: 0.0282 AC: 719 AN: 25452

European-Finnish (FIN) AF: 0.0352 AC: 777 AN: 22074

Middle Eastern (MID) AF: 0.0394 AC: 57 AN: 1448

European-Non Finnish (NFE) AF: 0.0395 AC: 7195 AN: 181954

Other (OTH) AF: 0.0497 AC: 920 AN: 18518

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0379 AC: 3797 AN: 100282 Hom.: 243 Cov.: 0 AF XY: 0.0379 AC XY: 1779 AN XY: 46898

African (AFR) AF: 0.158 AC: 3340 AN: 21202

American (AMR) AF: 0.0163 AC: 172 AN: 10520

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 61 AN: 2860

East Asian (EAS) AF: 0.00 AC: 0 AN: 3850

South Asian (SAS) AF: 0.00195 AC: 6 AN: 3084

European-Finnish (FIN) AF: 0.00407 AC: 21 AN: 5158

Middle Eastern (MID) AF: 0.00549 AC: 1 AN: 182

European-Non Finnish (NFE) AF: 0.00296 AC: 152 AN: 51426

Other (OTH) AF: 0.0261 AC: 36 AN: 1378

Alfa AF: 0.00109 Hom.: 1433

ClinVar

ClinVar submissions as Germline

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		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs56353515; hg19: chr16-31003962;