rs3093387

Positions:

• chr16-27449747-G-A

Variant summary

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

The NM_181078.3(IL21R):​c.*464G>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 0.166 in 241,522 control chromosomes in the GnomAD database, including 4,191 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 0.16 (2354 hom., cov: 33)
  • Exomes 𝑓: 0.18 (1837 hom.)
• Consequence: IL21R NM_181078.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3	c.*464G>A		3_prime_UTR_variant	9/9	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.*464G>A		3_prime_UTR_variant	9/9	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.*464G>A		3_prime_UTR_variant	9/9	1		ENSP00000379103.4
IL21R	ENST00000564089.5	c.*464G>A		3_prime_UTR_variant	10/10	5		ENSP00000456707.1
IL21R-AS1	ENST00000563191.1	n.537C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23712 AN: 152126 Hom.: 2354 Cov.: 33

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.183 AC: 16296 AN: 89278 Hom.: 1837 Cov.: 0 AF XY: 0.183 AC XY: 7590 AN XY: 41566

Gnomad4 AFR exome AF: 0.0483

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.000775

Gnomad4 SAS exome AF: 0.0552

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.227

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.156 AC: 23713 AN: 152244 Hom.: 2354 Cov.: 33 AF XY: 0.154 AC XY: 11451 AN XY: 74440

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.00404

Gnomad4 SAS AF: 0.0728

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.178

Alfa AF: 0.221 Hom.: 2164

Bravo AF: 0.154

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
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: rs3093387; hg19: chr16-27461068;