rs2072496

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000215.4(JAK3):c.1915-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,609,508 control chromosomes in the GnomAD database, including 10,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 959 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9626 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.40

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=-0.93).

BP6

Variant 19-17835245-G-A is Benign according to our data. Variant chr19-17835245-G-A is described in ClinVar as [Benign]. Clinvar id is 632862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
JAK3	NM_000215.4 link	c.1915-30C>T	intron_variant	Intron 14 of 23	ENST00000458235.7	NP_000206.2	P52333-1A0A024R7M7
JAK3	XM_047438786.1 link	c.1915-30C>T	intron_variant	Intron 14 of 23		XP_047294742.1
JAK3	XR_007066796.1 link	n.1965-30C>T	intron_variant	Intron 14 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 link	c.1915-30C>T		intron_variant	Intron 14 of 23	5	NM_000215.4	ENSP00000391676.1		P52333-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15779

AN:

152174

Hom.:

960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0985

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.0930

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.0545

Gnomad MID

AF:

0.121

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.0971

GnomAD3 exomes

AF:

0.113

AC:

27237

AN:

242044

Hom.:

1818

AF XY:

0.114

AC XY:

15084

AN XY:

132028

show subpopulations

Gnomad AFR exome

AF:

0.100

Gnomad AMR exome

AF:

0.0895

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.276

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0612

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.110

AC:

160496

AN:

1457218

Hom.:

9626

Cov.:

AF XY:

0.111

AC XY:

80326

AN XY:

724770

show subpopulations

Gnomad4 AFR exome

AF:

0.0989

Gnomad4 AMR exome

AF:

0.0882

Gnomad4 ASJ exome

AF:

0.0553

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.0584

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.104

AC:

15784

AN:

152290

Hom.:

959

Cov.:

AF XY:

0.102

AC XY:

7596

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0984

Gnomad4 AMR

AF:

0.0930

Gnomad4 ASJ

AF:

0.0576

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.140

Gnomad4 FIN

AF:

0.0545

Gnomad4 NFE

AF:

0.104

Gnomad4 OTH

AF:

0.0975

Alfa

AF:

0.103

Hom.:

478

Bravo

AF:

0.106

Asia WGS

AF:

0.184

AC:

639

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 28, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: The JAK3 c.1915-30C>T variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may alter ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 29715/269050 control chromosomes (1955 homozygotes)(gnomAD) at a frequency of 0.1104442, which is approximately 102 times the estimated maximal expected allele frequency of a pathogenic JAK3 variant (0.0010801), suggesting this variant is likely a benign polymorphism. This variant has been reported in 2 patients with SCID (Walshe 2009), however without strong evidence for causality. Taken together, this variant is classified as benign. -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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