Variant chr1-64835986-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002227.4(JAK1):c.3258+112G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 675,290 control chromosomes in the GnomAD database, including 68,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.52 ( 23604 hom., cov: 32)

Exomes 𝑓: 0.40 ( 45151 hom. )

Consequence

JAK1
NM_002227.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.845

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-64835986-C-A is Benign according to our data. Variant chr1-64835986-C-A is described in ClinVar as [Benign]. Clinvar id is 2688493.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 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.3258+112G>T		intron_variant		ENST00000342505.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK1	ENST00000342505.5 linkuse as main transcript	c.3258+112G>T		intron_variant		5	NM_002227.4	A1

Frequencies

GnomAD3 genomes

AF:

0.515

AC:

78104

AN:

151734

Hom.:

23546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.420

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.351

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.401

AC:

210097

AN:

523438

Hom.:

45151

AF XY:

0.395

AC XY:

110086

AN XY:

278370

show subpopulations

Gnomad4 AFR exome

AF:

0.841

Gnomad4 AMR exome

AF:

0.513

Gnomad4 ASJ exome

AF:

0.470

Gnomad4 EAS exome

AF:

0.594

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.404

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.430

GnomAD4 genome

AF:

0.515

AC:

78227

AN:

151852

Hom.:

23604

Cov.:

AF XY:

0.515

AC XY:

38174

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.840

Gnomad4 AMR

AF:

0.470

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.612

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.420

Gnomad4 NFE

AF:

0.351

Gnomad4 OTH

AF:

0.489

Alfa

AF:

0.470

Hom.:

2378

Bravo

AF:

0.538

Asia WGS

AF:

0.525

AC:

1824

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.40

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