Variant 19-17844192-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+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,535,870 control chromosomes in the GnomAD database, including 76,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10870 hom., cov: 32)

Exomes 𝑓: 0.30 ( 65214 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.254

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:

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=-0.8).

BP6

Variant 19-17844192-C-T is Benign according to our data. Variant chr19-17844192-C-T is described in ClinVar as [Benign]. Clinvar id is 1291547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
JAK3	NM_000215.4 linkuse as main transcript	c.184+42G>A	intron_variant	ENST00000458235.7
JAK3	XM_011527991.3 linkuse as main transcript	c.184+42G>A	intron_variant
JAK3	XM_047438786.1 linkuse as main transcript	c.184+42G>A	intron_variant
JAK3	XR_007066796.1 linkuse as main transcript	n.234+42G>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK3	ENST00000458235.7 linkuse as main transcript	c.184+42G>A		intron_variant		5	NM_000215.4	P1	P52333-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55343

AN:

151848

Hom.:

10860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.520

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.321

AC:

51482

AN:

160416

Hom.:

8536

AF XY:

0.318

AC XY:

27209

AN XY:

85566

show subpopulations

Gnomad AFR exome

AF:

0.514

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.340

Gnomad SAS exome

AF:

0.329

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.295

Gnomad OTH exome

AF:

0.323

GnomAD4 exome

AF:

0.304

AC:

420086

AN:

1383904

Hom.:

65214

Cov.:

AF XY:

0.304

AC XY:

207754

AN XY:

684336

show subpopulations

Gnomad4 AFR exome

AF:

0.523

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.344

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:

0.327

GnomAD4 genome

AF:

0.364

AC:

55391

AN:

151966

Hom.:

10870

Cov.:

AF XY:

0.362

AC XY:

26894

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.378

Alfa

AF:

0.322

Hom.:

4428

Bravo

AF:

0.382

Asia WGS

AF:

0.357

AC:

1241

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 53. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.7

DANN

Benign

0.73

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