19-17836600-A-G

Position:

• chr19-17836600-A-G

Variant summary

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

The NM_000215.4(JAK3):​c.1786+529T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 350,200 control chromosomes in the GnomAD database, including 30,261 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 0.43 (14078 hom., cov: 32)
  • Exomes 𝑓: 0.39 (16183 hom.)
• Consequence: JAK3 NM_000215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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 (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK3	NM_000215.4	c.1786+529T>C		intron_variant		ENST00000458235.7
JAK3	XM_011527991.3	c.*317T>C		3_prime_UTR_variant	14/14
JAK3	XM_047438786.1	c.1786+529T>C		intron_variant
JAK3	XR_007066796.1	n.1836+529T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK3	ENST00000458235.7	c.1786+529T>C		intron_variant		5	NM_000215.4	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64509 AN: 151792 Hom.: 14060 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.394 AC: 78189 AN: 198290 Hom.: 16183 AF XY: 0.393 AC XY: 39417 AN XY: 100420

Gnomad4 AFR exome AF: 0.520

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.554

Gnomad4 SAS exome AF: 0.384

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.425 AC: 64567 AN: 151910 Hom.: 14078 Cov.: 32 AF XY: 0.425 AC XY: 31540 AN XY: 74232

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.386

Gnomad4 OTH AF: 0.407

Alfa AF: 0.393 Hom.: 2373

Bravo AF: 0.427

Asia WGS AF: 0.438 AC: 1523 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	0.55
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3212762; hg19: chr19-17947409;