Variant rs12129819 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002227.4(JAK1):c.3096G>A(p.Lys1032Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,613,920 control chromosomes in the GnomAD database, including 7,594 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 566 hom., cov: 32)

Exomes 𝑓: 0.092 ( 7028 hom. )

Consequence

JAK1
NM_002227.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.53

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:

JAK1 (HGNC:):

JAK1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 1-64837976-C-T is Benign according to our data. Variant chr1-64837976-C-T is described in ClinVar as [Benign]. Clinvar id is 1168338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAK1	NM_002227.4 linkuse as main transcript	c.3096G>A	p.Lys1032Lys	synonymous_variant	22/25	ENST00000342505.5	NP_002218.2	P23458

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK1	ENST00000342505.5 linkuse as main transcript	c.3096G>A	p.Lys1032Lys	synonymous_variant	22/25	5	NM_002227.4	ENSP00000343204.4		P23458

Frequencies

GnomAD3 genomes

AF:

0.0763

AC:

11601

AN:

152116

Hom.:

566

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.0796

Gnomad ASJ

AF:

0.0934

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0871

GnomAD3 exomes

AF:

0.0766

AC:

19123

AN:

249512

Hom.:

999

AF XY:

0.0757

AC XY:

10252

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.0967

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0149

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0950

GnomAD4 exome

AF:

0.0916

AC:

133865

AN:

1461686

Hom.:

7028

Cov.:

AF XY:

0.0900

AC XY:

65441

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0323

Gnomad4 AMR exome

AF:

0.0572

Gnomad4 ASJ exome

AF:

0.0940

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0146

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.104

Gnomad4 OTH exome

AF:

0.0819

GnomAD4 genome

AF:

0.0761

AC:

11592

AN:

152234

Hom.:

566

Cov.:

AF XY:

0.0759

AC XY:

5650

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0340

Gnomad4 AMR

AF:

0.0794

Gnomad4 ASJ

AF:

0.0934

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.113

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0862

Alfa

AF:

0.0931

Hom.:

559

Bravo

AF:

0.0742

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.109

EpiControl

AF:

0.105

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

7.8

DANN

Benign

0.87

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