dbSNP rs3212711: JAK3:c.184+22C>T (chr19-17844212-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.184+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,564,852 control chromosomes in the GnomAD database, including 76,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10695 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66097 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.259

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=-0.91).

BP6

Variant 19-17844212-G-A is Benign according to our data. Variant chr19-17844212-G-A is described in ClinVar as [Benign]. Clinvar id is 1183811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
JAK3	NM_000215.4 link	c.184+22C>T	intron_variant	Intron 2 of 23	ENST00000458235.7	NP_000206.2	P52333-1A0A024R7M7
JAK3	XM_047438786.1 link	c.184+22C>T	intron_variant	Intron 2 of 23		XP_047294742.1
JAK3	XM_011527991.3 link	c.184+22C>T	intron_variant	Intron 2 of 13		XP_011526293.2
JAK3	XR_007066796.1 link	n.234+22C>T	intron_variant	Intron 2 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7 link	c.184+22C>T		intron_variant	Intron 2 of 23	5	NM_000215.4	ENSP00000391676.1		P52333-1

Frequencies

GnomAD3 genomes

AF:

0.362

AC:

54964

AN:

151840

Hom.:

10687

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.377

GnomAD3 exomes

AF:

0.317

AC:

57295

AN:

180778

Hom.:

9441

AF XY:

0.314

AC XY:

30528

AN XY:

97250

show subpopulations

Gnomad AFR exome

AF:

0.507

Gnomad AMR exome

AF:

0.338

Gnomad ASJ exome

AF:

0.357

Gnomad EAS exome

AF:

0.337

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.290

Gnomad OTH exome

AF:

0.320

GnomAD4 exome

AF:

0.303

AC:

427597

AN:

1412894

Hom.:

66097

Cov.:

AF XY:

0.303

AC XY:

211696

AN XY:

699278

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.346

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.336

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.293

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.362

AC:

55007

AN:

151958

Hom.:

10695

Cov.:

AF XY:

0.359

AC XY:

26693

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.509

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.327

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.295

Gnomad4 OTH

AF:

0.377

Alfa

AF:

0.336

Hom.:

2471

Bravo

AF:

0.379

Asia WGS

AF:

0.353

AC:

1230

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.89

DANN

Benign

0.48

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