rs7250423

Positions:

• chr19-17847808-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000215.4(JAK3):​c.-14+138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 239,806 control chromosomes in the GnomAD database, including 7,794 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (7224 hom., cov: 33)
  • Exomes 𝑓: 0.085 (570 hom.)
• Consequence: JAK3 NM_000215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.40

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAK3	NM_000215.4	c.-14+138G>A		intron_variant		ENST00000458235.7	NP_000206.2
JAK3	XM_011527991.3	c.-14+138G>A		intron_variant			XP_011526293.2
JAK3	XM_047438786.1	c.-45+138G>A		intron_variant			XP_047294742.1
JAK3	XR_007066796.1	n.37+138G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAK3	ENST00000458235.7	c.-14+138G>A		intron_variant		5	NM_000215.4	ENSP00000391676	P1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33362 AN: 152146 Hom.: 7205 Cov.: 33

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.0853 AC: 7468 AN: 87546 Hom.: 570 AF XY: 0.0818 AC XY: 3370 AN XY: 41208

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.0884

Gnomad4 EAS exome AF: 0.205

Gnomad4 SAS exome AF: 0.0699

Gnomad4 FIN exome AF: 0.0435

Gnomad4 NFE exome AF: 0.0632

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.220 AC: 33434 AN: 152260 Hom.: 7224 Cov.: 33 AF XY: 0.217 AC XY: 16125 AN XY: 74450

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0325

Gnomad4 NFE AF: 0.0737

Gnomad4 OTH AF: 0.194

Alfa AF: 0.104 Hom.: 1474

Bravo AF: 0.243

Asia WGS AF: 0.205 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.43
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7250423; hg19: chr19-17958617;