Genetic Variant IL21R:c.-106C>T (chr16-27402529-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181078.3(IL21R):c.-106C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 153,818 control chromosomes in the GnomAD database, including 953 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 0.095 ( 942 hom., cov: 32)

Exomes 𝑓: 0.093 ( 11 hom. )

Consequence

IL21R
NM_181078.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.892

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cryptosporidiosis-chronic cholangitis-liver disease syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

IL21R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.-106C>T	5_prime_UTR_variant	Exon 1 of 9	ENST00000337929.8	NP_851564.1	Q9HBE5
IL21R	NM_181079.5 link	c.-181C>T	5_prime_UTR_variant	Exon 1 of 10		NP_851565.4	Q9HBE5
IL21R	XM_011545857.4 link	c.-217C>T	5_prime_UTR_variant	Exon 1 of 10		XP_011544159.1
IL21R	XM_017023257.3 link	c.-236C>T	5_prime_UTR_variant	Exon 1 of 10		XP_016878746.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 link	c.-106C>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_181078.3	ENSP00000338010.3		Q9HBE5
IL21R	ENST00000564089.5 link	c.-247C>T		5_prime_UTR_variant	Exon 1 of 10	5		ENSP00000456707.1		Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.0953

AC:

14501

AN:

152134

Hom.:

943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0232

Gnomad AMI

AF:

0.114

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0205

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.0932

AC:

146

AN:

1566

Hom.:

Cov.:

AF XY:

0.0902

AC XY:

AN XY:

898

show subpopulations

African (AFR)

AF:

0.0833

AC:

AN:

American (AMR)

AF:

0.0377

AC:

AN:

318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0147

AC:

AN:

136

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.119

AC:

117

AN:

984

Other (OTH)

AF:

0.0909

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0952

AC:

14496

AN:

152252

Hom.:

942

Cov.:

AF XY:

0.0951

AC XY:

7079

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0231

AC:

960

AN:

41562

American (AMR)

AF:

0.0851

AC:

1301

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

441

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5184

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4828

European-Finnish (FIN)

AF:

0.184

AC:

1947

AN:

10590

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9391

AN:

68006

Other (OTH)

AF:

0.101

AC:

213

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

676

1353

2029

2706

3382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

607

Bravo

AF:

0.0840

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.4

(source)

DANN

Benign

0.77

PhyloP100

-0.89

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over