chr16-30992641-CG-C

Variant names:

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

Variant summary

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

The NM_052874.5(STX1B):​c.*179delC 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 0.76 (29376 hom., cov: 0)
  • Exomes 𝑓: 0.75 (85800 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-CG-C is Benign according to our data. Variant chr16-30992641-CG-C is described in ClinVar as Benign. ClinVar VariationId is 1267927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 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.*179delC		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.*179delC		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*179delC		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 76456 AN: 100434 Hom.: 29368 Cov.: 0

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.786

GnomAD4 exome AF: 0.754 AC: 232670 AN: 308642 Hom.: 85800 Cov.: 0 AF XY: 0.757 AC XY: 121605 AN XY: 160618

African (AFR) AF: 0.432 AC: 3944 AN: 9128

American (AMR) AF: 0.779 AC: 8677 AN: 11134

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 7596 AN: 10100

East Asian (EAS) AF: 0.925 AC: 21254 AN: 22978

South Asian (SAS) AF: 0.826 AC: 21282 AN: 25780

European-Finnish (FIN) AF: 0.766 AC: 17358 AN: 22646

Middle Eastern (MID) AF: 0.768 AC: 1137 AN: 1480

European-Non Finnish (NFE) AF: 0.738 AC: 137634 AN: 186448

Other (OTH) AF: 0.728 AC: 13788 AN: 18948

GnomAD4 genome AF: 0.761 AC: 76486 AN: 100482 Hom.: 29376 Cov.: 0 AF XY: 0.767 AC XY: 36065 AN XY: 47000

African (AFR) AF: 0.508 AC: 10851 AN: 21352

American (AMR) AF: 0.843 AC: 8888 AN: 10538

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 2310 AN: 2862

East Asian (EAS) AF: 0.970 AC: 3733 AN: 3850

South Asian (SAS) AF: 0.924 AC: 2849 AN: 3082

European-Finnish (FIN) AF: 0.850 AC: 4393 AN: 5168

Middle Eastern (MID) AF: 0.791 AC: 144 AN: 182

European-Non Finnish (NFE) AF: 0.812 AC: 41753 AN: 51446

Other (OTH) AF: 0.789 AC: 1090 AN: 1382

Alfa AF: 0.744 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)		0.050		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; COSMIC: COSV52679521; COSMIC: COSV52679521;