Variant 19-17826949-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.3208-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,594,644 control chromosomes in the GnomAD database, including 30,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5176 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24928 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.192

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:

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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 19-17826949-C-T is Benign according to our data. Variant chr19-17826949-C-T is described in ClinVar as [Benign]. Clinvar id is 1290849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAK3	NM_000215.4 linkuse as main transcript	c.3208-39G>A		intron_variant		ENST00000458235.7	NP_000206.2	P52333-1A0A024R7M7
JAK3	XM_047438786.1 linkuse as main transcript	c.3208-39G>A		intron_variant			XP_047294742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 linkuse as main transcript	c.3208-39G>A		intron_variant		5	NM_000215.4	ENSP00000391676.1		P52333-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35238

AN:

151960

Hom.:

5153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.212

GnomAD3 exomes

AF:

0.165

AC:

38952

AN:

235540

Hom.:

3988

AF XY:

0.162

AC XY:

20885

AN XY:

128602

show subpopulations

Gnomad AFR exome

AF:

0.422

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.0171

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.179

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.178

AC:

257393

AN:

1442566

Hom.:

24928

Cov.:

AF XY:

0.177

AC XY:

126571

AN XY:

716964

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.111

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.147

Gnomad4 NFE exome

AF:

0.183

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.232

AC:

35308

AN:

152078

Hom.:

5176

Cov.:

AF XY:

0.226

AC XY:

16770

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.202

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.138

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.194

Hom.:

1360

Bravo

AF:

0.241

Asia WGS

AF:

0.104

AC:

360

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 27% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

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