rs478665
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_001321852.2(JAK1):c.-78+17754T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0619 in 152,210 control chromosomes in the GnomAD database, including 537 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.062 ( 537 hom., cov: 32)
Consequence
JAK1
NM_001321852.2 intron
NM_001321852.2 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.769
Genes affected
JAK1 (HGNC:6190): (Janus kinase 1) This gene encodes a membrane protein that is a member of a class of protein-tyrosine kinases (PTK) characterized by the presence of a second phosphotransferase-related domain immediately N-terminal to the PTK domain. The encoded kinase phosphorylates STAT proteins (signal transducers and activators of transcription) and plays a key role in interferon-alpha/beta, interferon-gamma, and cytokine signal transduction. This gene plays a crucial role in effecting the expression of genes that mediate inflammation, epithelial remodeling, and metastatic cancer progression. This gene is a key component of the interleukin-6 (IL-6)/JAK1/STAT3 immune and inflammation response and is a therapeutic target for alleviating cytokine storms. The kinase activity of this gene is directly inhibited by the suppressor of cytokine signalling 1 (SOCS1) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JAK1 | NM_001321852.2 | c.-78+17754T>C | intron_variant | NP_001308781.1 | ||||
JAK1 | NM_001321853.2 | c.-162+16778T>C | intron_variant | NP_001308782.1 | ||||
JAK1 | NM_001321854.2 | c.-78+16778T>C | intron_variant | NP_001308783.1 | ||||
JAK1 | XM_047419676.1 | c.-78+17754T>C | intron_variant | XP_047275632.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JAK1 | ENST00000671954.2 | c.-180-5268T>C | intron_variant | ENSP00000500841 | A1 | |||||
JAK1 | ENST00000672099.1 | c.-384+17754T>C | intron_variant | ENSP00000500328 | ||||||
JAK1 | ENST00000672434.2 | c.-162+16778T>C | intron_variant | ENSP00000499900 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0618 AC: 9393AN: 152092Hom.: 534 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0619 AC: 9416AN: 152210Hom.: 537 Cov.: 32 AF XY: 0.0636 AC XY: 4736AN XY: 74424
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at