rs202021264
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2
The NM_002227.4(JAK1):c.184A>G(p.Ile62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,614,016 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 2 hom. )
Consequence
JAK1
NM_002227.4 missense
NM_002227.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 1.89
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, JAK1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008037269).
BP6
?
Variant 1-64883298-T-C is Benign according to our data. Variant chr1-64883298-T-C is described in ClinVar as [Benign]. Clinvar id is 134548.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 65 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAK1 | NM_002227.4 | c.184A>G | p.Ile62Val | missense_variant | 3/25 | ENST00000342505.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAK1 | ENST00000342505.5 | c.184A>G | p.Ile62Val | missense_variant | 3/25 | 5 | NM_002227.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000427 AC: 65AN: 152206Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
65
AN:
152206
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000725 AC: 180AN: 248442Hom.: 1 AF XY: 0.000675 AC XY: 91AN XY: 134808
GnomAD3 exomes
AF:
AC:
180
AN:
248442
Hom.:
AF XY:
AC XY:
91
AN XY:
134808
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000489 AC: 715AN: 1461692Hom.: 2 Cov.: 31 AF XY: 0.000481 AC XY: 350AN XY: 727124
GnomAD4 exome
AF:
AC:
715
AN:
1461692
Hom.:
Cov.:
31
AF XY:
AC XY:
350
AN XY:
727124
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000427 AC: 65AN: 152324Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32AN XY: 74496
GnomAD4 genome
?
AF:
AC:
65
AN:
152324
Hom.:
Cov.:
32
AF XY:
AC XY:
32
AN XY:
74496
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
5
ExAC
?
AF:
AC:
74
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at