rs3093390

Variant names:

• chr16-27452127-C-T
• rs3093390
• ENST00000563191.1:n.477+616G>A

Variant summary

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

The ENST00000563191.1(IL21R-AS1):​n.477+616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 186,520 control chromosomes in the GnomAD database, including 6,581 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 (5590 hom., cov: 32)
  • Exomes 𝑓: 0.23 (991 hom.)
• Consequence: IL21R-AS1 ENST00000563191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

Genes affected

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

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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 rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.*2844C>T		downstream_gene_variant		ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R-AS1	ENST00000563191.1	n.477+616G>A		intron_variant	Intron 2 of 2	2
IL21R	ENST00000337929.8	c.*2844C>T		downstream_gene_variant		1	NM_181078.3	ENSP00000338010.3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39763 AN: 151892 Hom.: 5562 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.230 AC: 7931 AN: 34512 Hom.: 991 AF XY: 0.230 AC XY: 3667 AN XY: 15916

Gnomad4 AFR exome AF: 0.380

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.0797

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.262 AC: 39820 AN: 152008 Hom.: 5590 Cov.: 32 AF XY: 0.258 AC XY: 19166 AN XY: 74300

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.255

Alfa AF: 0.241 Hom.: 2600

Bravo AF: 0.273

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3093390; hg19: chr16-27463448;