5-55941107-C-T
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002184.4(IL6ST):c.2732G>A(p.Arg911Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
IL6ST
NM_002184.4 missense
NM_002184.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 2.80
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 Likely_benign. Variant got -2 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.24669912).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IL6ST | NM_002184.4 | c.2732G>A | p.Arg911Gln | missense_variant | 17/17 | ENST00000381298.7 | NP_002175.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
IL6ST | ENST00000381298.7 | c.2732G>A | p.Arg911Gln | missense_variant | 17/17 | 1 | NM_002184.4 | ENSP00000370698.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250686Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135458
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GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461208Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726858
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 911 of the IL6ST protein (p.Arg911Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with IL6ST-related conditions. ClinVar contains an entry for this variant (Variation ID: 1505497). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.;N
REVEL
Benign
Sift
Uncertain
D;D;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;.
Vest4
MutPred
Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);Loss of MoRF binding (P = 0.0033);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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