Variant rs3212780 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.3207+75C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,056,466 control chromosomes in the GnomAD database, including 34,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3927 hom., cov: 32)

Exomes 𝑓: 0.25 ( 30397 hom. )

Consequence

JAK3
NM_000215.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.69

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 19-17830033-G-A is Benign according to our data. Variant chr19-17830033-G-A is described in ClinVar as [Benign]. Clinvar id is 1283176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-17830033-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.273 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.3207+75C>T		intron_variant		ENST00000458235.7	NP_000206.2
JAK3	XM_047438786.1 linkuse as main transcript	c.3207+75C>T		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.3207+75C>T		intron_variant		5	NM_000215.4	ENSP00000391676	P1	P52333-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31159

AN:

152080

Hom.:

3929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0774

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.253

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.217

GnomAD3 exomes

AF:

0.212

AC:

29325

AN:

138050

Hom.:

3672

AF XY:

0.216

AC XY:

16257

AN XY:

75296

show subpopulations

Gnomad AFR exome

AF:

0.0722

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.0237

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.310

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.250

AC:

225729

AN:

904268

Hom.:

30397

Cov.:

AF XY:

0.248

AC XY:

115322

AN XY:

464788

show subpopulations

Gnomad4 AFR exome

AF:

0.0722

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.0234

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.299

Gnomad4 NFE exome

AF:

0.277

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.205

AC:

31157

AN:

152198

Hom.:

3927

Cov.:

AF XY:

0.207

AC XY:

15381

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0771

Gnomad4 AMR

AF:

0.208

Gnomad4 ASJ

AF:

0.253

Gnomad4 EAS

AF:

0.0272

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.277

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.222

Hom.:

829

Bravo

AF:

0.192

Asia WGS

AF:

0.0990

AC:

345

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	Jul 25, 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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.77

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