rs1373998
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002184.4(IL6ST):c.973+665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 751,860 control chromosomes in the GnomAD database, including 13,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.24 ( 6916 hom., cov: 32)
Exomes 𝑓: 0.13 ( 6841 hom. )
Consequence
IL6ST
NM_002184.4 intron
NM_002184.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.381
Genes affected
IL6ST (HGNC:6021): (interleukin 6 cytokine family signal transducer) The protein encoded by this gene is a signal transducer shared by many cytokines, including interleukin 6 (IL6), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM). This protein functions as a part of the cytokine receptor complex. The activation of this protein is dependent upon the binding of cytokines to their receptors. vIL6, a protein related to IL6 and encoded by the Kaposi sarcoma-associated herpesvirus, can bypass the interleukin 6 receptor (IL6R) and directly activate this protein. Knockout studies in mice suggest that this gene plays a critical role in regulating myocyte apoptosis. Alternatively spliced transcript variants have been described. A related pseudogene has been identified on chromosome 17. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
?
Variant 5-55959737-G-A is Benign according to our data. Variant chr5-55959737-G-A is described in ClinVar as [Benign]. Clinvar id is 2688475.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL6ST | NM_002184.4 | c.973+665C>T | intron_variant | ENST00000381298.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL6ST | ENST00000381298.7 | c.973+665C>T | intron_variant | 1 | NM_002184.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.240 AC: 36548AN: 151984Hom.: 6894 Cov.: 32
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GnomAD4 exome AF: 0.132 AC: 79253AN: 599758Hom.: 6841 AF XY: 0.128 AC XY: 40219AN XY: 313122
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GnomAD4 genome ? AF: 0.241 AC: 36625AN: 152102Hom.: 6916 Cov.: 32 AF XY: 0.233 AC XY: 17360AN XY: 74362
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Jan 24, 2024 | This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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