rs12934152

chr16-27403018-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:2
• Conservation: PhyloP100: 0.260

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1247564.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
IL21R	NM_181078.3	c.-17+400T>C		intron_variant		ENST00000337929.8
IL21R	NM_181079.5	c.-91-62T>C		intron_variant
IL21R	XM_011545857.4	c.-127-26T>C		intron_variant
IL21R	XM_017023257.3	c.-147+400T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.-17+400T>C		intron_variant		1	NM_181078.3	P1
IL21R	ENST00000564089.5	c.-157-62T>C		intron_variant		5		P1

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

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.0125

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.218

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

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.0137

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.223

Alfa AF: 0.221 Hom.: 2045

Bravo AF: 0.167

Asia WGS AF: 0.0840 AC: 292 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Increased circulating IgE level Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2003

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.5
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs12934152; hg19: chr16-27414339;