rs2285452

Variant names:

• chr16-27449576-G-A
• rs2285452
• NM_181078.3:c.*293G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):​c.*293G>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 0.234 in 474,030 control chromosomes in the GnomAD database, including 14,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5628 hom., cov: 33)
  • Exomes 𝑓: 0.22 (8535 hom.)
• Consequence: IL21R NM_181078.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.78
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-27449576-G-A is Benign according to our data. Variant chr16-27449576-G-A is described in ClinVar as Benign. ClinVar VariationId is 1278126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.*293G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.*293G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.*293G>A		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000379103.4
IL21R-AS1	ENST00000563191.1	n.708C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
IL21R	ENST00000564089.5	c.*293G>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39892 AN: 152040 Hom.: 5600 Cov.: 33

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.245

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: 0.258

GnomAD4 exome AF: 0.220 AC: 70798 AN: 321872 Hom.: 8535 Cov.: 0 AF XY: 0.214 AC XY: 35452 AN XY: 165452

African (AFR) AF: 0.386 AC: 4056 AN: 10510

American (AMR) AF: 0.234 AC: 2482 AN: 10594

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 2859 AN: 11098

East Asian (EAS) AF: 0.126 AC: 3022 AN: 23912

South Asian (SAS) AF: 0.115 AC: 2949 AN: 25720

European-Finnish (FIN) AF: 0.182 AC: 3785 AN: 20818

Middle Eastern (MID) AF: 0.237 AC: 361 AN: 1526

European-Non Finnish (NFE) AF: 0.236 AC: 46681 AN: 198008

Other (OTH) AF: 0.234 AC: 4603 AN: 19686

GnomAD4 genome AF: 0.263 AC: 39950 AN: 152158 Hom.: 5628 Cov.: 33 AF XY: 0.258 AC XY: 19232 AN XY: 74404

African (AFR) AF: 0.379 AC: 15706 AN: 41480

American (AMR) AF: 0.243 AC: 3714 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 852 AN: 3472

East Asian (EAS) AF: 0.106 AC: 548 AN: 5170

South Asian (SAS) AF: 0.117 AC: 564 AN: 4828

European-Finnish (FIN) AF: 0.170 AC: 1803 AN: 10598

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

European-Non Finnish (NFE) AF: 0.234 AC: 15923 AN: 67992

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.246 Hom.: 13900

Bravo AF: 0.273

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		-5.8
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: rs2285452; hg19: chr16-27460897;