16-30989573-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_052874.5(STX1B):c.*3248A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 152,338 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (11 hom., cov: 33)
  • Exomes 𝑓: 0.011 (1 hom.)
• Consequence: STX1B NM_052874.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.849

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 16-30989573-T-C is Benign according to our data. Variant chr16-30989573-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2498187.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 916 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STX1B	NM_052874.5	c.*3248A>G		3_prime_UTR_variant	10/10	ENST00000215095.11
STX1B	XM_017022893.2	c.*3248A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STX1B	ENST00000215095.11	c.*3248A>G		3_prime_UTR_variant	10/10	1	NM_052874.5	P1

Frequencies

GnomAD3 genomes AF: 0.00603 AC: 916 AN: 151950 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.000943

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0329

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00753

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.0111 AC: 3 AN: 270 Hom.: 1 Cov.: 0 AF XY: 0.0109 AC XY: 2 AN XY: 184

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.00633

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00602 AC: 916 AN: 152068 Hom.: 11 Cov.: 33 AF XY: 0.00651 AC XY: 484 AN XY: 74336

Gnomad4 AFR AF: 0.000940

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0329

Gnomad4 NFE AF: 0.00753

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0102 Hom.: 2

Bravo AF: 0.00328

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neonatal hemochromatosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust

Mar 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	13
Dann	Benign	0.68

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: rs117126734; hg19: chr16-31000894;