rs2239928

Positions:

• chr16-27449880-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181078.3(IL21R):​c.*597C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 233,496 control chromosomes in the GnomAD database, including 7,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5615 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2300 hom.)
• Consequence: IL21R NM_181078.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.64

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]

IL21R-AS1 (HGNC:27551): (IL21R antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.*597C>A		3_prime_UTR_variant	9/9	ENST00000337929.8
IL21R-AS1	NR_037158.1	n.478-74G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.*597C>A		3_prime_UTR_variant	9/9	1	NM_181078.3	P1
IL21R	ENST00000395754.4	c.*597C>A		3_prime_UTR_variant	9/9	1		P1
IL21R-AS1	ENST00000563191.1	n.478-74G>T		intron_variant, non_coding_transcript_variant		2
IL21R	ENST00000564089.5	c.*597C>A		3_prime_UTR_variant	10/10	5		P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39843 AN: 152012 Hom.: 5587 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.231 AC: 18757 AN: 81366 Hom.: 2300 Cov.: 0 AF XY: 0.230 AC XY: 8629 AN XY: 37474

Gnomad4 AFR exome AF: 0.374

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0932

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.262 AC: 39901 AN: 152130 Hom.: 5615 Cov.: 33 AF XY: 0.258 AC XY: 19226 AN XY: 74404

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.257

Alfa AF: 0.244 Hom.: 4560

Bravo AF: 0.273

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.081
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239928; hg19: chr16-27461201;