Genetic Variant IL21R:c.-16-8642C>T (chr16-27421414-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.-16-8642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 148,370 control chromosomes in the GnomAD database, including 9,965 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 0.36 ( 9965 hom., cov: 29)

Consequence

IL21R
NM_181078.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0720

Publications

6 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=-0.93).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.-16-8642C>T	intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1	Q9HBE5
IL21R	NM_181079.5 link	c.51-8642C>T	intron_variant	Intron 2 of 9		NP_851565.4	Q9HBE5
IL21R	XM_011545857.4 link	c.51-8642C>T	intron_variant	Intron 2 of 9		XP_011544159.1
IL21R	XM_017023257.3 link	c.-17+5135C>T	intron_variant	Intron 2 of 9		XP_016878746.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 link	c.-16-8642C>T		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3		Q9HBE5
IL21R	ENST00000564089.5 link	c.-16-8642C>T		intron_variant	Intron 2 of 9	5		ENSP00000456707.1		Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

53579

AN:

148280

Hom.:

9957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.350

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

GnomAD4 genome

AF:

0.361

AC:

53617

AN:

148370

Hom.:

9965

Cov.:

AF XY:

0.368

AC XY:

26522

AN XY:

72008

show subpopulations

African (AFR)

AF:

0.398

AC:

16085

AN:

40460

American (AMR)

AF:

0.378

AC:

5617

AN:

14862

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

952

AN:

3442

East Asian (EAS)

AF:

0.513

AC:

2588

AN:

5040

South Asian (SAS)

AF:

0.503

AC:

2364

AN:

4704

European-Finnish (FIN)

AF:

0.362

AC:

3366

AN:

9308

Middle Eastern (MID)

AF:

0.350

AC:

100

AN:

286

European-Non Finnish (NFE)

AF:

0.320

AC:

21541

AN:

67306

Other (OTH)

AF:

0.353

AC:

726

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1651

3302

4954

6605

8256

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.342

Hom.:

6295

Bravo

AF:

0.358

Asia WGS

AF:

0.485

AC:

1683

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.33

(source)

DANN

Benign

0.62

PhyloP100

-0.072

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