NM_181078.3:c.-16-5599T>C

Variant names:

• chr16-27424457-T-C
• rs9930086
• NM_181078.3:c.-16-5599T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181078.3(IL21R):​c.-16-5599T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 151,988 control chromosomes in the GnomAD database, including 10,135 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 (10135 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.-16-5599T>C		intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1
IL21R	NM_181079.5	c.51-5599T>C		intron_variant	Intron 2 of 9		NP_851565.4
IL21R	XM_011545857.4	c.51-5599T>C		intron_variant	Intron 2 of 9		XP_011544159.1
IL21R	XM_017023257.3	c.-16-5599T>C		intron_variant	Intron 2 of 9		XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.-16-5599T>C		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000564089.5	c.-16-5599T>C		intron_variant	Intron 2 of 9	5		ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54382 AN: 151870 Hom.: 10126 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.358 AC: 54420 AN: 151988 Hom.: 10135 Cov.: 32 AF XY: 0.364 AC XY: 27040 AN XY: 74288

African (AFR) AF: 0.391 AC: 16179 AN: 41406

American (AMR) AF: 0.374 AC: 5707 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2752 AN: 5176

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4814

European-Finnish (FIN) AF: 0.345 AC: 3645 AN: 10564

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21690 AN: 67970

Other (OTH) AF: 0.351 AC: 740 AN: 2108

Alfa AF: 0.332 Hom.: 36129

Bravo AF: 0.359

Asia WGS AF: 0.494 AC: 1718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.78
PhyloP100		0.023
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: rs9930086; hg19: chr16-27435778;