rs56002407

Positions:

chr16-27449133-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000337929.8(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
ENST00000337929.8 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.623

Variant links:

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 links:

IL21R-AS1 (HGNC:27551): (IL21R antisense RNA 1)

IL21R-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3 linkuse as main transcript	c.1467G>A	p.Thr489=	synonymous_variant	9/9	ENST00000337929.8	NP_851564.1
IL21R-AS1	NR_037158.1 linkuse as main transcript	n.1151C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IL21R	ENST00000337929.8 linkuse as main transcript	c.1467G>A	p.Thr489=	synonymous_variant	9/9	1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4 linkuse as main transcript	c.1467G>A	p.Thr489=	synonymous_variant	9/9	1		ENSP00000379103	P1
IL21R-AS1	ENST00000563191.1 linkuse as main transcript	n.1151C>T		non_coding_transcript_exon_variant	3/3	2
IL21R	ENST00000564089.5 linkuse as main transcript	c.1467G>A	p.Thr489=	synonymous_variant	10/10	5		ENSP00000456707	P1

Frequencies

GnomAD3 genomes

AF:

0.00163

AC:

248

AN:

152220

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00105

AC XY:

143

AN XY:

135576

show subpopulations

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.:

Cov.:

AF XY:

0.00192

AC XY:

1392

AN XY:

726872

show subpopulations

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.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74488

show subpopulations

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.:

Bravo

AF:

0.00170

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over