rs200049537
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_002227.4(JAK1):c.1078C>T(p.Arg360Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000139 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R360Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002227.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK1 | NM_002227.4 | c.1078C>T | p.Arg360Trp | missense_variant | 8/25 | ENST00000342505.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK1 | ENST00000342505.5 | c.1078C>T | p.Arg360Trp | missense_variant | 8/25 | 5 | NM_002227.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152136Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000144 AC: 36AN: 249468Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135354
GnomAD4 exome AF: 0.000147 AC: 215AN: 1461332Hom.: 0 Cov.: 30 AF XY: 0.000139 AC XY: 101AN XY: 727020
GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152254Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74450
ClinVar
Submissions by phenotype
Autoinflammation, immune dysregulation, and eosinophilia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 07, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 360 of the JAK1 protein (p.Arg360Trp). This variant is present in population databases (rs200049537, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with JAK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 134549). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at