rs3212745

chr19-17839698-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000215.4(JAK3):c.1255-35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00356 in 1,487,386 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (74 hom., cov: 30)
  • Exomes 𝑓: 0.0020 (72 hom.)
• Consequence: JAK3 NM_000215.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-17839698-C-T is Benign according to our data. Variant chr19-17839698-C-T is described in ClinVar as [Benign]. Clinvar id is 1222486.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAK3	NM_000215.4	c.1255-35G>A		intron_variant		ENST00000458235.7
JAK3	XM_011527991.3	c.1255-35G>A		intron_variant
JAK3	XM_047438786.1	c.1255-35G>A		intron_variant
JAK3	XR_007066796.1	n.1305-35G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAK3	ENST00000458235.7	c.1255-35G>A		intron_variant		5	NM_000215.4	P1

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2631 AN: 144968 Hom.: 74 Cov.: 30

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00651

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.00795

GnomAD3 exomes AF: 0.00501 AC: 1037 AN: 207170 Hom.: 32 AF XY: 0.00379 AC XY: 423 AN XY: 111754

Gnomad AFR exome AF: 0.0711

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000635

Gnomad SAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000349

Gnomad OTH exome AF: 0.00191

GnomAD4 exome AF: 0.00198 AC: 2661 AN: 1342332 Hom.: 72 Cov.: 24 AF XY: 0.00169 AC XY: 1132 AN XY: 671034

Gnomad4 AFR exome AF: 0.0753

Gnomad4 AMR exome AF: 0.00336

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000517

Gnomad4 SAS exome AF: 0.000161

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00466

GnomAD4 genome AF: 0.0182 AC: 2635 AN: 145054 Hom.: 74 Cov.: 30 AF XY: 0.0173 AC XY: 1227 AN XY: 70920

Gnomad4 AFR AF: 0.0709

Gnomad4 AMR AF: 0.00650

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000339

Gnomad4 OTH AF: 0.00787

Alfa AF: 0.0149 Hom.: 5

Bravo AF: 0.0208

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	4.1
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3212745; hg19: chr19-17950507;