Variant chr19-17844194-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000215.4(JAK3):c.184+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,539,842 control chromosomes in the GnomAD database, including 85,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 15594 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69850 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

JAK3 (HGNC:6193): (Janus kinase 3) The protein encoded by this gene is a member of the Janus kinase (JAK) family of tyrosine kinases involved in cytokine receptor-mediated intracellular signal transduction. It is predominantly expressed in immune cells and transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors. Mutations in this gene are associated with autosomal SCID (severe combined immunodeficiency disease). [provided by RefSeq, Jul 2008]

JAK3 links:

JAK3 (HGNC:):

JAK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-17844194-C-T is Benign according to our data. Variant chr19-17844194-C-T is described in ClinVar as [Benign]. Clinvar id is 1291546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
JAK3	NM_000215.4 linkuse as main transcript	c.184+40G>A	intron_variant	ENST00000458235.7	NP_000206.2	P52333-1A0A024R7M7
JAK3	XM_047438786.1 linkuse as main transcript	c.184+40G>A	intron_variant		XP_047294742.1
JAK3	XM_011527991.3 linkuse as main transcript	c.184+40G>A	intron_variant		XP_011526293.2
JAK3	XR_007066796.1 linkuse as main transcript	n.234+40G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 linkuse as main transcript	c.184+40G>A		intron_variant		5	NM_000215.4	ENSP00000391676.1		P52333-1

Frequencies

GnomAD3 genomes

AF:

0.416

AC:

63238

AN:

151832

Hom.:

15562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.420

GnomAD3 exomes

AF:

0.333

AC:

54007

AN:

162192

Hom.:

9739

AF XY:

0.327

AC XY:

28287

AN XY:

86562

show subpopulations

Gnomad AFR exome

AF:

0.702

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.330

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.309

AC:

429415

AN:

1387892

Hom.:

69850

Cov.:

AF XY:

0.309

AC XY:

211770

AN XY:

686182

show subpopulations

Gnomad4 AFR exome

AF:

0.711

Gnomad4 AMR exome

AF:

0.358

Gnomad4 ASJ exome

AF:

0.346

Gnomad4 EAS exome

AF:

0.338

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.294

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.417

AC:

63319

AN:

151950

Hom.:

15594

Cov.:

AF XY:

0.412

AC XY:

30622

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.699

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.420

Alfa

AF:

0.359

Hom.:

2048

Bravo

AF:

0.442

Asia WGS

AF:

0.371

AC:

1290

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

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 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.4

DANN

Benign

0.63

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