rs138046858

Variant names:

• chr16-30992550-G-A
• rs138046858
• NM_052874.5:c.*271C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-30992550-G-A
• chr16-30992550-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 979 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.*271C>T		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.*271C>T		3_prime_UTR	Exon 10 of 10	ENSP00000215095.5	P61266-1
	STX1B	ENST00000916717.1		c.*271C>T		3_prime_UTR	Exon 10 of 10	ENSP00000586776.1

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

African (AFR) AF: 0.0195 AC: 166 AN: 8492

American (AMR) AF: 0.00259 AC: 25 AN: 9636

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 270 AN: 9178

East Asian (EAS) AF: 0.00 AC: 0 AN: 20914

South Asian (SAS) AF: 0.000148 AC: 4 AN: 26942

European-Finnish (FIN) AF: 0.0000534 AC: 1 AN: 18722

Middle Eastern (MID) AF: 0.00384 AC: 5 AN: 1302

European-Non Finnish (NFE) AF: 0.000351 AC: 59 AN: 168156

Other (OTH) AF: 0.00376 AC: 64 AN: 17012

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

African (AFR) AF: 0.0185 AC: 766 AN: 41362

American (AMR) AF: 0.00328 AC: 50 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000530 AC: 36 AN: 67944

Other (OTH) AF: 0.00521 AC: 11 AN: 2110

Alfa AF: 0.00523 Hom.: 1

Bravo AF: 0.00725

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.4
DANN	Benign	0.78
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs138046858; hg19: chr16-31003871;