rs2239928

Variant names:

• chr16-27449880-C-A
• rs2239928
• NM_181078.3:c.*597C>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.*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
• Publications: 15 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=-0.96).
• 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: 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.*597C>A		3_prime_UTR	Exon 9 of 9	NP_851564.1
	IL21R	NM_181079.5		c.*597C>A		3_prime_UTR	Exon 10 of 10	NP_851565.4
	IL21R	NM_021798.4		c.*597C>A		3_prime_UTR	Exon 9 of 9	NP_068570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.*597C>A		3_prime_UTR	Exon 9 of 9	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.*597C>A		3_prime_UTR	Exon 9 of 9	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.*597C>A		3_prime_UTR	Exon 10 of 10	ENSP00000456707.1

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

African (AFR) AF: 0.374 AC: 1452 AN: 3882

American (AMR) AF: 0.226 AC: 585 AN: 2590

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 1312 AN: 5110

East Asian (EAS) AF: 0.138 AC: 1571 AN: 11374

South Asian (SAS) AF: 0.0932 AC: 68 AN: 730

European-Finnish (FIN) AF: 0.197 AC: 13 AN: 66

Middle Eastern (MID) AF: 0.261 AC: 128 AN: 490

European-Non Finnish (NFE) AF: 0.237 AC: 11936 AN: 50348

Other (OTH) AF: 0.250 AC: 1692 AN: 6776

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

African (AFR) AF: 0.378 AC: 15676 AN: 41468

American (AMR) AF: 0.242 AC: 3700 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3470

East Asian (EAS) AF: 0.106 AC: 546 AN: 5168

South Asian (SAS) AF: 0.117 AC: 566 AN: 4832

European-Finnish (FIN) AF: 0.170 AC: 1806 AN: 10602

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15921 AN: 67996

Other (OTH) AF: 0.257 AC: 542 AN: 2110

Alfa AF: 0.249 Hom.: 6275

Bravo AF: 0.273

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.081
DANN	Benign	0.55
PhyloP100		-5.6
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: rs2239928; hg19: chr16-27461201;