rs3093387

Variant names:

• chr16-27449747-G-A
• rs3093387
• NM_181078.3:c.*464G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.*464G>A		3_prime_UTR	Exon 9 of 9	NP_851564.1
	IL21R-AS1	NR_037158.1		n.537C>T		non_coding_transcript_exon	Exon 3 of 3
	IL21R	NM_181079.5		c.*464G>A		3_prime_UTR	Exon 10 of 10	NP_851565.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.*464G>A		3_prime_UTR	Exon 9 of 9	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.*464G>A		3_prime_UTR	Exon 9 of 9	ENSP00000379103.4
	IL21R-AS1	ENST00000563191.1	TSL:2	n.537C>T		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.0483 AC: 198 AN: 4100

American (AMR) AF: 0.174 AC: 717 AN: 4120

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 1276 AN: 5254

East Asian (EAS) AF: 0.000775 AC: 9 AN: 11616

South Asian (SAS) AF: 0.0552 AC: 77 AN: 1396

European-Finnish (FIN) AF: 0.136 AC: 38 AN: 280

Middle Eastern (MID) AF: 0.236 AC: 119 AN: 504

European-Non Finnish (NFE) AF: 0.227 AC: 12457 AN: 54880

Other (OTH) AF: 0.197 AC: 1405 AN: 7128

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

African (AFR) AF: 0.0428 AC: 1777 AN: 41562

American (AMR) AF: 0.197 AC: 3006 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 808 AN: 3466

East Asian (EAS) AF: 0.00404 AC: 21 AN: 5192

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4824

European-Finnish (FIN) AF: 0.168 AC: 1784 AN: 10604

Middle Eastern (MID) AF: 0.247 AC: 72 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15319 AN: 67990

Other (OTH) AF: 0.178 AC: 376 AN: 2112

Alfa AF: 0.208 Hom.: 2948

Bravo AF: 0.154

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.55
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093387; hg19: chr16-27461068;