rs796053349
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_003165.6(STXBP1):c.1548-7_1548-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000265 in 1,613,906 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00017 ( 2 hom. )
Consequence
STXBP1
NM_003165.6 splice_region, splice_polypyrimidine_tract, intron
NM_003165.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.348
Genes affected
STXBP1 (HGNC:11444): (syntaxin binding protein 1) This gene encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. Mutations in this gene have been associated with infantile epileptic encephalopathy-4. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 9-127682395-CTCTT-C is Benign according to our data. Variant chr9-127682395-CTCTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 207411.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 = 0.0012 (183/152340) while in subpopulation AFR AF= 0.00423 (176/41576). AF 95% confidence interval is 0.00372. There are 0 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 183 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STXBP1 | NM_001032221.6 | c.1548-7_1548-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000373299.5 | |||
STXBP1 | NM_003165.6 | c.1548-7_1548-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000373302.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STXBP1 | ENST00000373299.5 | c.1548-7_1548-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001032221.6 | A1 | |||
STXBP1 | ENST00000373302.8 | c.1548-7_1548-4del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003165.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00120 AC: 183AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000279 AC: 70AN: 250880Hom.: 0 AF XY: 0.000214 AC XY: 29AN XY: 135774
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GnomAD4 exome AF: 0.000168 AC: 245AN: 1461566Hom.: 2 AF XY: 0.000172 AC XY: 125AN XY: 727088
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 02, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2013 | The variant is found in INFANT-EPI panel(s). - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 15, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Early infantile epileptic encephalopathy with suppression bursts Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | STXBP1: BS1, BS2 - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at