19-7647539-G-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_006949.4(STXBP2):c.1696+28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,573,874 control chromosomes in the GnomAD database, including 96,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.35 ( 9250 hom., cov: 31)
Exomes 𝑓: 0.35 ( 86779 hom. )
Consequence
STXBP2
NM_006949.4 intron
NM_006949.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.63
Genes affected
STXBP2 (HGNC:11445): (syntaxin binding protein 2) This gene encodes a member of the STXBP/unc-18/SEC1 family. The encoded protein is involved in intracellular trafficking, control of SNARE (soluble NSF attachment protein receptor) complex assembly, and the release of cytotoxic granules by natural killer cells. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 19-7647539-G-C is Benign according to our data. Variant chr19-7647539-G-C is described in ClinVar as [Benign]. Clinvar id is 260100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.346 AC: 52567AN: 151830Hom.: 9232 Cov.: 31
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GnomAD3 exomes AF: 0.336 AC: 64667AN: 192400Hom.: 10956 AF XY: 0.332 AC XY: 34622AN XY: 104176
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GnomAD4 exome AF: 0.348 AC: 494449AN: 1421926Hom.: 86779 Cov.: 50 AF XY: 0.345 AC XY: 243285AN XY: 704192
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GnomAD4 genome AF: 0.346 AC: 52615AN: 151948Hom.: 9250 Cov.: 31 AF XY: 0.348 AC XY: 25833AN XY: 74266
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 46. Only high quality variants are reported. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2021 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Familial hemophagocytic lymphohistiocytosis 5 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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