rs3093363

Positions:

• chr16-27443241-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):​c.507+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 788,610 control chromosomes in the GnomAD database, including 38,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9559 hom., cov: 30)
  • Exomes 𝑓: 0.29 (29310 hom.)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.292

Genes affected

IL21R (HGNC:6006): (interleukin 21 receptor) The protein encoded by this gene is a cytokine receptor for interleukin 21 (IL21). It belongs to the type I cytokine receptors, and has been shown to form a heterodimeric receptor complex with the common gamma-chain, a receptor subunit also shared by the receptors for interleukin 2, 4, 7, 9, and 15. This receptor transduces the growth promoting signal of IL21, and is important for the proliferation and differentiation of T cells, B cells, and natural killer (NK) cells. The ligand binding of this receptor leads to the activation of multiple downstream signaling molecules, including JAK1, JAK3, STAT1, and STAT3. Knockout studies of a similar gene in mouse suggest a role for this gene in regulating immunoglobulin production. Three alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2010]

LOC124903668 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 16-27443241-A-G is Benign according to our data. Variant chr16-27443241-A-G is described in ClinVar as [Benign]. Clinvar id is 1271815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.507+125A>G		intron_variant		ENST00000337929.8
LOC124903668	XR_007065031.1	n.134-130T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.507+125A>G		intron_variant		1	NM_181078.3	P1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52162 AN: 151736 Hom.: 9524 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.290 AC: 184918 AN: 636756 Hom.: 29310 AF XY: 0.284 AC XY: 91902 AN XY: 323592

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.344 AC: 52234 AN: 151854 Hom.: 9559 Cov.: 30 AF XY: 0.344 AC XY: 25525 AN XY: 74222

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.323

Alfa AF: 0.309 Hom.: 14538

Bravo AF: 0.346

Asia WGS AF: 0.157 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.88
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3093363; hg19: chr16-27454562;