Genetic Variant IL21R:c.-16-9485C>T (chr16-27420571-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.-16-9485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 152,042 control chromosomes in the GnomAD database, including 9,884 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 0.35 ( 9884 hom., cov: 32)

Consequence

IL21R
NM_181078.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.243

Publications

2 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:

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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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
IL21R	NM_181078.3 link	c.-16-9485C>T	intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1
IL21R	NM_181079.5 link	c.51-9485C>T	intron_variant	Intron 2 of 9		NP_851565.4
IL21R	XM_011545857.4 link	c.51-9485C>T	intron_variant	Intron 2 of 9		XP_011544159.1
IL21R	XM_017023257.3 link	c.-17+4292C>T	intron_variant	Intron 2 of 9		XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 link	c.-16-9485C>T		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000564089.5 link	c.-16-9485C>T		intron_variant	Intron 2 of 9	5		ENSP00000456707.1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53631

AN:

151924

Hom.:

9877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.393

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.266

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.353

AC:

53669

AN:

152042

Hom.:

9884

Cov.:

AF XY:

0.359

AC XY:

26706

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.393

AC:

16304

AN:

41434

American (AMR)

AF:

0.373

AC:

5701

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.266

AC:

921

AN:

3468

East Asian (EAS)

AF:

0.506

AC:

2614

AN:

5170

South Asian (SAS)

AF:

0.493

AC:

2375

AN:

4818

European-Finnish (FIN)

AF:

0.339

AC:

3580

AN:

10574

Middle Eastern (MID)

AF:

0.342

AC:

100

AN:

292

European-Non Finnish (NFE)

AF:

0.310

AC:

21069

AN:

67994

Other (OTH)

AF:

0.345

AC:

729

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1748

3496

5243

6991

8739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.330

Hom.:

1136

Bravo

AF:

0.354

Asia WGS

AF:

0.487

AC:

1693

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.8

(source)

DANN

Benign

0.51

PhyloP100

-0.24

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over