rs12934152

Variant names:

• chr16-27403018-T-C
• rs12934152
• NM_181078.3:c.-17+400T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):​c.-17+400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 433,330 control chromosomes in the GnomAD database, including 9,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2937 hom., cov: 32)
  • Exomes 𝑓: 0.20 (6607 hom.)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.260
• Publications: 13 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-27403018-T-C is Benign according to our data. Variant chr16-27403018-T-C is described in ClinVar as Benign. ClinVar VariationId is 1247564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.-17+400T>C		intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1
IL21R	NM_181079.5	c.-91-62T>C		intron_variant	Intron 1 of 9		NP_851565.4
IL21R	XM_011545857.4	c.-127-26T>C		intron_variant	Intron 1 of 9		XP_011544159.1
IL21R	XM_017023257.3	c.-147+400T>C		intron_variant	Intron 1 of 9		XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.-17+400T>C		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000564089.5	c.-157-62T>C		intron_variant	Intron 1 of 9	5		ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26086 AN: 152090 Hom.: 2937 Cov.: 32

Gnomad AFR AF: 0.0512

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.199 AC: 56064 AN: 281122 Hom.: 6607 AF XY: 0.196 AC XY: 30000 AN XY: 152806

African (AFR) AF: 0.0503 AC: 433 AN: 8602

American (AMR) AF: 0.133 AC: 3058 AN: 22970

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 3162 AN: 8908

East Asian (EAS) AF: 0.0125 AC: 191 AN: 15222

South Asian (SAS) AF: 0.132 AC: 6631 AN: 50096

European-Finnish (FIN) AF: 0.166 AC: 1708 AN: 10268

Middle Eastern (MID) AF: 0.270 AC: 720 AN: 2662

European-Non Finnish (NFE) AF: 0.250 AC: 36976 AN: 147788

Other (OTH) AF: 0.218 AC: 3185 AN: 14606

GnomAD4 genome AF: 0.171 AC: 26080 AN: 152208 Hom.: 2937 Cov.: 32 AF XY: 0.165 AC XY: 12281 AN XY: 74440

African (AFR) AF: 0.0511 AC: 2124 AN: 41540

American (AMR) AF: 0.172 AC: 2622 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3468

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5186

South Asian (SAS) AF: 0.124 AC: 600 AN: 4830

European-Finnish (FIN) AF: 0.164 AC: 1738 AN: 10606

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17117 AN: 67972

Other (OTH) AF: 0.223 AC: 472 AN: 2114

Alfa AF: 0.218 Hom.: 8602

Bravo AF: 0.167

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 12700598, 17015683) -

Increased circulating IgE concentration Benign:1

Apr 01, 2003

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.68
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12934152; hg19: chr16-27414339;