rs3830585
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_139276.3(STAT3):c.1601-8_1601-7insT 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 0.231 in 1,613,038 control chromosomes in the GnomAD database, including 53,571 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.34 ( 12220 hom., cov: 0)
Exomes 𝑓: 0.22 ( 41351 hom. )
Consequence
STAT3
NM_139276.3 splice_region, splice_polypyrimidine_tract, intron
NM_139276.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.765
Genes affected
STAT3 (HGNC:11364): (signal transducer and activator of transcription 3) The protein encoded by this gene is a member of the STAT protein family. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated through phosphorylation in response to various cytokines and growth factors including IFNs, EGF, IL5, IL6, HGF, LIF and BMP2. This protein mediates the expression of a variety of genes in response to cell stimuli, and thus plays a key role in many cellular processes such as cell growth and apoptosis. The small GTPase Rac1 has been shown to bind and regulate the activity of this protein. PIAS3 protein is a specific inhibitor of this protein. This gene also plays a role in regulating host response to viral and bacterial infections. Mutations in this gene are associated with infantile-onset multisystem autoimmune disease and hyper-immunoglobulin E syndrome. [provided by RefSeq, Aug 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-42323632-G-GA is Benign according to our data. Variant chr17-42323632-G-GA is described in ClinVar as [Benign]. Clinvar id is 165294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STAT3 | NM_139276.3 | c.1601-8_1601-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000264657.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STAT3 | ENST00000264657.10 | c.1601-8_1601-7insT | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_139276.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.338 AC: 51335AN: 151992Hom.: 12179 Cov.: 0
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GnomAD3 exomes AF: 0.246 AC: 61687AN: 250758Hom.: 9911 AF XY: 0.244 AC XY: 33060AN XY: 135576
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GnomAD4 exome AF: 0.220 AC: 320944AN: 1460928Hom.: 41351 Cov.: 32 AF XY: 0.222 AC XY: 161210AN XY: 726838
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GnomAD4 genome ? AF: 0.338 AC: 51437AN: 152110Hom.: 12220 Cov.: 0 AF XY: 0.338 AC XY: 25095AN XY: 74352
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ClinVar
Significance: Benign
Submissions summary: Benign:9Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 30, 2013 | Benign based on high population prevalence - |
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 35% of patients studied by a panel of primary immunodeficiencies. Number of patients: 34. Only high quality variants are reported. - |
not provided Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 08, 2018 | - - |
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. - |
STAT3-related early-onset multisystem autoimmune disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
STAT3-related early-onset multisystem autoimmune disease;CN031130:Hyper-IgE recurrent infection syndrome 1, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 06, 2022 | - - |
STAT3 gain of function;CN031130:Hyper-IgE recurrent infection syndrome 1, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hyper-IgE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Hyper-IgE recurrent infection syndrome 1, autosomal dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 15, 2021 | - - |
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