rs56002407

chr16-27449133-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_181078.3(IL21R):c.1467G>A(p.Thr489=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,440 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: IL21R NM_181078.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.623

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-27449133-G-A is Benign according to our data. Variant chr16-27449133-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 540995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-27449133-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.623 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.1467G>A	p.Thr489=	synonymous_variant	9/9	ENST00000337929.8
IL21R-AS1	NR_037158.1	n.1151C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.1467G>A	p.Thr489=	synonymous_variant	9/9	1	NM_181078.3	P1
IL21R	ENST00000395754.4	c.1467G>A	p.Thr489=	synonymous_variant	9/9	1		P1
IL21R-AS1	ENST00000563191.1	n.1151C>T		non_coding_transcript_exon_variant	3/3	2
IL21R	ENST00000564089.5	c.1467G>A	p.Thr489=	synonymous_variant	10/10	5		P1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00103 AC: 258 AN: 250062 Hom.: 0 AF XY: 0.00105 AC XY: 143 AN XY: 135576

Gnomad AFR exome AF: 0.00257

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.00202 AC: 2949 AN: 1461102 Hom.: 3 Cov.: 31 AF XY: 0.00192 AC XY: 1392 AN XY: 726872

Gnomad4 AFR exome AF: 0.00236

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.000209

Gnomad4 NFE exome AF: 0.00248

Gnomad4 OTH exome AF: 0.00137

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.00136 AC XY: 101 AN XY: 74488

Gnomad4 AFR AF: 0.00190

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00228

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00170

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	IL21R: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 06, 2019	- -

Cryptosporidiosis-chronic cholangitis-liver disease syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	2.6
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs56002407; hg19: chr16-27460454;