rs3093390

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

IL21R Gene-Disease associations (from GenCC):

• immunodeficiency disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cryptosporidiosis-chronic cholangitis-liver disease syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000563191.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R-AS1	NR_037158.1		n.477+616G>A		intron	N/A
	IL21R	NM_181078.3	MANE Select	c.*2844C>T		downstream_gene	N/A	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.*2844C>T		downstream_gene	N/A	NP_851565.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R-AS1	ENST00000563191.1	TSL:2	n.477+616G>A		intron	N/A
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.*2844C>T		downstream_gene	N/A	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000871346.1		c.*2844C>T		downstream_gene	N/A	ENSP00000541405.1

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

African (AFR) AF: 0.380 AC: 455 AN: 1196

American (AMR) AF: 0.234 AC: 203 AN: 868

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 557 AN: 2160

East Asian (EAS) AF: 0.136 AC: 884 AN: 6480

South Asian (SAS) AF: 0.0797 AC: 22 AN: 276

European-Finnish (FIN) AF: 0.286 AC: 8 AN: 28

Middle Eastern (MID) AF: 0.241 AC: 51 AN: 212

European-Non Finnish (NFE) AF: 0.247 AC: 5052 AN: 20434

Other (OTH) AF: 0.245 AC: 699 AN: 2858

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

African (AFR) AF: 0.378 AC: 15647 AN: 41422

American (AMR) AF: 0.242 AC: 3701 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3466

East Asian (EAS) AF: 0.106 AC: 546 AN: 5164

South Asian (SAS) AF: 0.115 AC: 553 AN: 4810

European-Finnish (FIN) AF: 0.170 AC: 1805 AN: 10592

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.234 AC: 15898 AN: 67964

Other (OTH) AF: 0.255 AC: 537 AN: 2108

Alfa AF: 0.242 Hom.: 9939

Bravo AF: 0.273

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.39
PhyloP100		-1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3093390;

hg19: chr16-27463448;