Variant rs45598436 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002227.4(JAK1):c.579T>C(p.Ala193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 1,613,434 control chromosomes in the GnomAD database, including 7,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.078 ( 577 hom., cov: 32)

Exomes 𝑓: 0.093 ( 7175 hom. )

Consequence

JAK1
NM_002227.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.07

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]

JAK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-64869379-A-G is Benign according to our data. Variant chr1-64869379-A-G is described in ClinVar as [Benign]. Clinvar id is 1168339.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK1	NM_002227.4 linkuse as main transcript	c.579T>C	p.Ala193=	synonymous_variant	6/25	ENST00000342505.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK1	ENST00000342505.5 linkuse as main transcript	c.579T>C	p.Ala193=	synonymous_variant	6/25	5	NM_002227.4	A1

Frequencies

GnomAD3 genomes

AF:

0.0776

AC:

11808

AN:

152086

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0793

Gnomad ASJ

AF:

0.0948

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.0860

GnomAD3 exomes

AF:

0.0775

AC:

19326

AN:

249384

Hom.:

1005

AF XY:

0.0764

AC XY:

10334

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.0543

Gnomad ASJ exome

AF:

0.0975

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.109

Gnomad OTH exome

AF:

0.0958

GnomAD4 exome

AF:

0.0926

AC:

135296

AN:

1461230

Hom.:

7175

Cov.:

AF XY:

0.0910

AC XY:

66161

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0371

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.0946

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0146

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.0830

GnomAD4 genome

AF:

0.0775

AC:

11803

AN:

152204

Hom.:

577

Cov.:

AF XY:

0.0769

AC XY:

5722

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0378

Gnomad4 AMR

AF:

0.0791

Gnomad4 ASJ

AF:

0.0948

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0127

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.0851

Alfa

AF:

0.0934

Hom.:

448

Bravo

AF:

0.0758

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.110

EpiControl

AF:

0.106

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.68

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over