rs3212711

Variant names:

• chr19-17844212-G-A
• rs3212711
• NM_000215.4:c.184+22C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-17844212-G-A
• chr19-17844212-G-C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 0.259
• Publications: 17 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	NM_000215.4	MANE Select	c.184+22C>T		intron	N/A	NP_000206.2
	JAK3	NM_001440439.1		c.184+22C>T		intron	N/A	NP_001427368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAK3	ENST00000458235.7	TSL:5 MANE Select	c.184+22C>T		intron	N/A	ENSP00000391676.1
	JAK3	ENST00000527670.5	TSL:1	c.184+22C>T		intron	N/A	ENSP00000432511.1
	JAK3	ENST00000534444.1	TSL:1	c.184+22C>T		intron	N/A	ENSP00000436421.1

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

GnomAD2 exomes AF: 0.317 AC: 57295 AN: 180778 AF XY: 0.314

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 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

African (AFR) AF: 0.511 AC: 16466 AN: 32254

American (AMR) AF: 0.346 AC: 13054 AN: 37718

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8700 AN: 25298

East Asian (EAS) AF: 0.336 AC: 12510 AN: 37226

South Asian (SAS) AF: 0.330 AC: 26663 AN: 80812

European-Finnish (FIN) AF: 0.228 AC: 11249 AN: 49348

Middle Eastern (MID) AF: 0.314 AC: 1323 AN: 4216

European-Non Finnish (NFE) AF: 0.293 AC: 318609 AN: 1087542

Other (OTH) AF: 0.325 AC: 19023 AN: 58480

GnomAD4 genome AF: 0.362 AC: 55007 AN: 151958 Hom.: 10695 Cov.: 32 AF XY: 0.359 AC XY: 26693 AN XY: 74286

African (AFR) AF: 0.509 AC: 21105 AN: 41440

American (AMR) AF: 0.380 AC: 5795 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1717 AN: 5138

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4820

European-Finnish (FIN) AF: 0.221 AC: 2333 AN: 10572

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20034 AN: 67940

Other (OTH) AF: 0.377 AC: 795 AN: 2106

Alfa AF: 0.365 Hom.: 5803

Bravo AF: 0.379

Asia WGS AF: 0.353 AC: 1230 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.89
DANN	Benign	0.48
PhyloP100		0.26
PromoterAI		0.016	Neutral
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: rs3212711; hg19: chr19-17955021; COSMIC: COSV71685729;