dbSNP rs2285452: IL21R:c.*293G>A (chr16-27449576-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181078.3(IL21R):c.*293G>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 0.234 in 474,030 control chromosomes in the GnomAD database, including 14,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5628 hom., cov: 33)

Exomes 𝑓: 0.22 ( 8535 hom. )

Consequence

IL21R
NM_181078.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -5.78

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-27449576-G-A is Benign according to our data. Variant chr16-27449576-G-A is described in ClinVar as [Benign]. Clinvar id is 1278126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.*293G>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.*293G>A	3_prime_UTR_variant	Exon 9 of 9	1	NM_181078.3	ENSP00000338010.3	Q9HBE5
IL21R	ENST00000395754.4 link	c.*293G>A	3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000379103.4	Q9HBE5
IL21R	ENST00000564089.5 link	c.*293G>A	3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000456707.1	Q9HBE5
IL21R-AS1	ENST00000563191.1 link	n.708C>T	non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39892

AN:

152040

Hom.:

5600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.231

Gnomad AMR

AF:

0.243

Gnomad ASJ

AF:

0.245

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:

0.258

GnomAD4 exome

AF:

0.220

AC:

70798

AN:

321872

Hom.:

8535

Cov.:

AF XY:

0.214

AC XY:

35452

AN XY:

165452

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.126

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.182

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.263

AC:

39950

AN:

152158

Hom.:

5628

Cov.:

AF XY:

0.258

AC XY:

19232

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.379

Gnomad4 AMR

AF:

0.243

Gnomad4 ASJ

AF:

0.245

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.258

Alfa

AF:

0.240

Hom.:

7651

Bravo

AF:

0.273

Asia WGS

AF:

0.143

AC:

498

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over