dbSNP rs2239928: IL21R:c.*597C>A (chr16-27449880-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_181078.3(IL21R):c.*597C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 233,496 control chromosomes in the GnomAD database, including 7,915 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 ( 5615 hom., cov: 33)

Exomes 𝑓: 0.23 ( 2300 hom. )

Consequence

IL21R
NM_181078.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.64

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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.*597C>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000337929.8	NP_851564.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL21R	ENST00000337929.8 link	c.*597C>A	3_prime_UTR_variant	Exon 9 of 9	1	NM_181078.3	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4 link	c.*597C>A	3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5 link	c.*597C>A	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000456707.1	Q9HBE5
IL21R-AS1	ENST00000563191.1 link	n.478-74G>T	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39843

AN:

152012

Hom.:

5587

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.257

GnomAD4 exome

AF:

0.231

AC:

18757

AN:

81366

Hom.:

2300

Cov.:

AF XY:

0.230

AC XY:

8629

AN XY:

37474

show subpopulations

Gnomad4 AFR exome

AF:

0.374

Gnomad4 AMR exome

AF:

0.226

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.0932

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.237

Gnomad4 OTH exome

AF:

0.250

GnomAD4 genome

AF:

0.262

AC:

39901

AN:

152130

Hom.:

5615

Cov.:

AF XY:

0.258

AC XY:

19226

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.378

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.244

Hom.:

4560

Bravo

AF:

0.273

Asia WGS

AF:

0.133

AC:

462

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.081

DANN

Benign

0.55

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over