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rs3790532

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002227.4(JAK1):​c.3140+225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 152,284 control chromosomes in the GnomAD database, including 342 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 0.027 ( 342 hom., cov: 33)

Consequence

JAK1
NM_002227.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109
Variant links:
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 = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
JAK1NM_002227.4 linkuse as main transcriptc.3140+225C>T intron_variant ENST00000342505.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
JAK1ENST00000342505.5 linkuse as main transcriptc.3140+225C>T intron_variant 5 NM_002227.4 A1

Frequencies

GnomAD3 genomes
AF:
0.0273
AC:
4156
AN:
152166
Hom.:
340
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00690
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0835
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.288
Gnomad SAS
AF:
0.0794
Gnomad FIN
AF:
0.00820
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.00789
Gnomad OTH
AF:
0.0339
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0274
AC:
4165
AN:
152284
Hom.:
342
Cov.:
33
AF XY:
0.0302
AC XY:
2245
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.00688
Gnomad4 AMR
AF:
0.0844
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.287
Gnomad4 SAS
AF:
0.0796
Gnomad4 FIN
AF:
0.00820
Gnomad4 NFE
AF:
0.00788
Gnomad4 OTH
AF:
0.0341
Alfa
AF:
0.0290
Hom.:
46
Bravo
AF:
0.0349
Asia WGS
AF:
0.177
AC:
613
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.8
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3790532; hg19: chr1-65303390; API