Genetic Variant IL21R-AS1:n.477+616G>A (chr16-27452127-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 ENST00000563191.1(IL21R-AS1):n.477+616G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 186,520 control chromosomes in the GnomAD database, including 6,581 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 0.26 ( 5590 hom., cov: 32)

Exomes 𝑓: 0.23 ( 991 hom. )

Consequence

IL21R-AS1
ENST00000563191.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

16 publications found

Variant links:

Genes affected

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

IL21R-AS1 links:

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.*2844C>T		downstream_gene_variant		ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R-AS1	ENST00000563191.1 link	n.477+616G>A		intron_variant	Intron 2 of 2	2
IL21R	ENST00000337929.8 link	c.*2844C>T		downstream_gene_variant		1	NM_181078.3	ENSP00000338010.3		Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39763

AN:

151892

Hom.:

5562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.245

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.230

AC:

7931

AN:

34512

Hom.:

991

AF XY:

0.230

AC XY:

3667

AN XY:

15916

show subpopulations

African (AFR)

AF:

0.380

AC:

455

AN:

1196

American (AMR)

AF:

0.234

AC:

203

AN:

868

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

557

AN:

2160

East Asian (EAS)

AF:

0.136

AC:

884

AN:

6480

South Asian (SAS)

AF:

0.0797

AC:

AN:

276

European-Finnish (FIN)

AF:

0.286

AC:

AN:

Middle Eastern (MID)

AF:

0.241

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.247

AC:

5052

AN:

20434

Other (OTH)

AF:

0.245

AC:

699

AN:

2858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

290

580

869

1159

1449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.262

AC:

39820

AN:

152008

Hom.:

5590

Cov.:

AF XY:

0.258

AC XY:

19166

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.378

AC:

15647

AN:

41422

American (AMR)

AF:

0.242

AC:

3701

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

849

AN:

3466

East Asian (EAS)

AF:

0.106

AC:

546

AN:

5164

South Asian (SAS)

AF:

0.115

AC:

553

AN:

4810

European-Finnish (FIN)

AF:

0.170

AC:

1805

AN:

10592

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.234

AC:

15898

AN:

67964

Other (OTH)

AF:

0.255

AC:

537

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1444

2888

4333

5777

7221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.242

Hom.:

9939

Bravo

AF:

0.273

Asia WGS

AF:

0.132

AC:

460

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.64

(source)

DANN

Benign

0.39

PhyloP100

-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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16-27452127-C-T

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