dbSNP rs3212741: JAK3:c.1143-28C>T (chr19-17840369-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000215.4(JAK3):c.1143-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,453,662 control chromosomes in the GnomAD database, including 31,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2359 hom., cov: 30)

Exomes 𝑓: 0.20 ( 28830 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.43

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=-0.82).

BP6

Variant 19-17840369-G-A is Benign according to our data. Variant chr19-17840369-G-A is described in ClinVar as [Benign]. Clinvar id is 1221017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
JAK3	NM_000215.4 link	c.1143-28C>T	intron_variant	Intron 8 of 23	ENST00000458235.7	NP_000206.2	P52333-1A0A024R7M7
JAK3	XM_047438786.1 link	c.1143-28C>T	intron_variant	Intron 8 of 23		XP_047294742.1
JAK3	XM_011527991.3 link	c.1143-28C>T	intron_variant	Intron 8 of 13		XP_011526293.2
JAK3	XR_007066796.1 link	n.1193-28C>T	intron_variant	Intron 8 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 link	c.1143-28C>T		intron_variant	Intron 8 of 23	5	NM_000215.4	ENSP00000391676.1		P52333-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23642

AN:

151872

Hom.:

2360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.0480

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.175

GnomAD3 exomes

AF:

0.169

AC:

39859

AN:

236188

Hom.:

3822

AF XY:

0.173

AC XY:

22077

AN XY:

127976

show subpopulations

Gnomad AFR exome

AF:

0.0392

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.194

Gnomad EAS exome

AF:

0.0449

Gnomad SAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.204

AC:

265752

AN:

1301672

Hom.:

28830

Cov.:

AF XY:

0.202

AC XY:

132491

AN XY:

654784

show subpopulations

Gnomad4 AFR exome

AF:

0.0390

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.0481

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.218

Gnomad4 NFE exome

AF:

0.227

Gnomad4 OTH exome

AF:

0.189

GnomAD4 genome

AF:

0.156

AC:

23635

AN:

151990

Hom.:

2359

Cov.:

AF XY:

0.153

AC XY:

11392

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0429

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.0476

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.213

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.173

Alfa

AF:

0.199

Hom.:

1624

Bravo

AF:

0.145

Asia WGS

AF:

0.0980

AC:

340

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

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 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

-0.82

CADD

Benign

3.2

DANN

Benign

0.70

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