rs3212711

chr19-17844212-G-Achr19-17844212-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.259

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK3	NM_000215.4	c.184+22C>T		intron_variant		ENST00000458235.7
JAK3	XM_011527991.3	c.184+22C>T		intron_variant
JAK3	XM_047438786.1	c.184+22C>T		intron_variant
JAK3	XR_007066796.1	n.234+22C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK3	ENST00000458235.7	c.184+22C>T		intron_variant		5	NM_000215.4	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54964 AN: 151840 Hom.: 10687 Cov.: 32

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

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.: 31 AF XY: 0.303 AC XY: 211696 AN XY: 699278

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.: 32 AF XY: 0.359 AC XY: 26693 AN XY: 74286

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

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

Other links and lift over

dbSNP: rs3212711; hg19: chr19-17955021; COSMIC: COSV71685729; COSMIC: COSV71685729;