rs2072496

Variant names:

• chr19-17835245-G-A
• rs2072496
• NM_000215.4:c.1915-30C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-17835245-G-A
• chr19-17835245-G-T

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.1915-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,609,508 control chromosomes in the GnomAD database, including 10,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (959 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9626 hom.)
• Consequence: JAK3 NM_000215.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.40
• Publications: 19 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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-17835245-G-A is Benign according to our data. Variant chr19-17835245-G-A is described in ClinVar as Benign. ClinVar VariationId is 632862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 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.1915-30C>T		intron	N/A	NP_000206.2
	JAK3	NM_001440439.1		c.1915-30C>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.1915-30C>T		intron	N/A	ENSP00000391676.1	P52333-1
	JAK3	ENST00000527670.5	TSL:1	c.1915-30C>T		intron	N/A	ENSP00000432511.1	P52333-1
	JAK3	ENST00000534444.1	TSL:1	c.1915-30C>T		intron	N/A	ENSP00000436421.1	P52333-2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15779 AN: 152174 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0971

GnomAD2 exomes AF: 0.113 AC: 27237 AN: 242044 AF XY: 0.114

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0895

Gnomad ASJ exome AF: 0.0571

Gnomad EAS exome AF: 0.276

Gnomad FIN exome AF: 0.0612

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.110 AC: 160496 AN: 1457218 Hom.: 9626 Cov.: 39 AF XY: 0.111 AC XY: 80326 AN XY: 724770

African (AFR) AF: 0.0989 AC: 3306 AN: 33436

American (AMR) AF: 0.0882 AC: 3923 AN: 44460

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 1440 AN: 26044

East Asian (EAS) AF: 0.261 AC: 10337 AN: 39628

South Asian (SAS) AF: 0.138 AC: 11923 AN: 86120

European-Finnish (FIN) AF: 0.0584 AC: 2979 AN: 51008

Middle Eastern (MID) AF: 0.130 AC: 720 AN: 5544

European-Non Finnish (NFE) AF: 0.107 AC: 118762 AN: 1110736

Other (OTH) AF: 0.118 AC: 7106 AN: 60242

GnomAD4 genome AF: 0.104 AC: 15784 AN: 152290 Hom.: 959 Cov.: 32 AF XY: 0.102 AC XY: 7596 AN XY: 74462

African (AFR) AF: 0.0984 AC: 4087 AN: 41548

American (AMR) AF: 0.0930 AC: 1424 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1403 AN: 5178

South Asian (SAS) AF: 0.140 AC: 678 AN: 4828

European-Finnish (FIN) AF: 0.0545 AC: 579 AN: 10624

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7084 AN: 68020

Other (OTH) AF: 0.0975 AC: 206 AN: 2112

Alfa AF: 0.105 Hom.: 857

Bravo AF: 0.106

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-1.4
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: rs2072496; hg19: chr19-17946054; COSMIC: COSV71685824; COSMIC: COSV71685824;