19-17836600-A-G

Variant names:

• chr19-17836600-A-G
• rs3212762
• NM_000215.4:c.1786+529T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• T-B+ severe combined immunodeficiency due to JAK3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	NM_000215.4	MANE Select	c.1786+529T>C		intron	N/A	NP_000206.2
	JAK3	NM_001440439.1		c.1786+529T>C		intron	N/A	NP_001427368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	ENST00000458235.7	TSL:5 MANE Select	c.1786+529T>C		intron	N/A	ENSP00000391676.1
	JAK3	ENST00000527670.5	TSL:1	c.1786+529T>C		intron	N/A	ENSP00000432511.1
	JAK3	ENST00000534444.1	TSL:1	c.1786+529T>C		intron	N/A	ENSP00000436421.1

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

African (AFR) AF: 0.520 AC: 3805 AN: 7320

American (AMR) AF: 0.306 AC: 2247 AN: 7338

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 2432 AN: 7840

East Asian (EAS) AF: 0.554 AC: 9051 AN: 16326

South Asian (SAS) AF: 0.384 AC: 8504 AN: 22128

European-Finnish (FIN) AF: 0.352 AC: 1838 AN: 5220

Middle Eastern (MID) AF: 0.370 AC: 337 AN: 912

European-Non Finnish (NFE) AF: 0.380 AC: 45058 AN: 118602

Other (OTH) AF: 0.390 AC: 4917 AN: 12604

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

African (AFR) AF: 0.523 AC: 21654 AN: 41416

American (AMR) AF: 0.359 AC: 5482 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1095 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2917 AN: 5146

South Asian (SAS) AF: 0.389 AC: 1868 AN: 4806

European-Finnish (FIN) AF: 0.378 AC: 3992 AN: 10562

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26224 AN: 67932

Other (OTH) AF: 0.407 AC: 861 AN: 2116

Alfa AF: 0.393 Hom.: 21603

Bravo AF: 0.427

Asia WGS AF: 0.438 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.55
DANN	Benign	0.72
PhyloP100		-0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3212762; hg19: chr19-17947409;