rs2228043
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002184.4(IL6ST):c.1189C>G(p.Leu397Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,611,530 control chromosomes in the GnomAD database, including 15,056 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_002184.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IL6ST | NM_002184.4 | c.1189C>G | p.Leu397Val | missense_variant | 10/17 | ENST00000381298.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IL6ST | ENST00000381298.7 | c.1189C>G | p.Leu397Val | missense_variant | 10/17 | 1 | NM_002184.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.174 AC: 26455AN: 152022Hom.: 3085 Cov.: 32
GnomAD3 exomes AF: 0.119 AC: 29908AN: 251324Hom.: 2327 AF XY: 0.115 AC XY: 15629AN XY: 135834
GnomAD4 exome AF: 0.120 AC: 175672AN: 1459390Hom.: 11952 Cov.: 30 AF XY: 0.119 AC XY: 86232AN XY: 726234
GnomAD4 genome ? AF: 0.174 AC: 26517AN: 152140Hom.: 3104 Cov.: 32 AF XY: 0.170 AC XY: 12625AN XY: 74396
ClinVar
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 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. - |
IL6ST-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 05, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at