rs3212756

Variant names:

• chr19-17837038-G-T
• rs3212756
• NM_000215.4:c.1786+91C>A

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.1786+91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 836,798 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (481 hom., cov: 30)
  • Exomes 𝑓: 0.0055 (247 hom.)
• Consequence: JAK3 NM_000215.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.00
• Publications: 4 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=-0.99).
• BP6: Variant 19-17837038-G-T is Benign according to our data. Variant chr19-17837038-G-T is described in ClinVar as Benign. ClinVar VariationId is 1281410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.152 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.1786+91C>A		intron	N/A	NP_000206.2
	JAK3	NM_001440439.1		c.1786+91C>A		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.1786+91C>A		intron	N/A	ENSP00000391676.1	P52333-1
	JAK3	ENST00000527670.5	TSL:1	c.1786+91C>A		intron	N/A	ENSP00000432511.1	P52333-1
	JAK3	ENST00000534444.1	TSL:1	c.1786+91C>A		intron	N/A	ENSP00000436421.1	P52333-2

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6498 AN: 143734 Hom.: 476 Cov.: 30

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000464

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.000453

Gnomad OTH AF: 0.0350

GnomAD2 exomes AF: 0.00905 AC: 1246 AN: 137606 AF XY: 0.00686

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.00812

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000363

Gnomad OTH exome AF: 0.00413

GnomAD4 exome AF: 0.00552 AC: 3825 AN: 692956 Hom.: 247 Cov.: 10 AF XY: 0.00443 AC XY: 1616 AN XY: 364692

African (AFR) AF: 0.160 AC: 2866 AN: 17962

American (AMR) AF: 0.00994 AC: 335 AN: 33714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19556

East Asian (EAS) AF: 0.00 AC: 0 AN: 29432

South Asian (SAS) AF: 0.000335 AC: 22 AN: 65594

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 39938

Middle Eastern (MID) AF: 0.00653 AC: 17 AN: 2602

European-Non Finnish (NFE) AF: 0.000366 AC: 165 AN: 450688

Other (OTH) AF: 0.0125 AC: 419 AN: 33470

GnomAD4 genome AF: 0.0453 AC: 6520 AN: 143842 Hom.: 481 Cov.: 30 AF XY: 0.0441 AC XY: 3069 AN XY: 69524

African (AFR) AF: 0.156 AC: 6148 AN: 39500

American (AMR) AF: 0.0195 AC: 267 AN: 13690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 4564

South Asian (SAS) AF: 0.000464 AC: 2 AN: 4308

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8906

Middle Eastern (MID) AF: 0.0106 AC: 3 AN: 284

European-Non Finnish (NFE) AF: 0.000453 AC: 30 AN: 66280

Other (OTH) AF: 0.0347 AC: 70 AN: 2018

Alfa AF: 0.0267 Hom.: 38

Bravo AF: 0.0496

Asia WGS AF: 0.00982 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.69
PhyloP100		-1.0
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: rs3212756; hg19: chr19-17947847;