NM_181078.3:c.50-1176A>G

Variant names:

• chr16-27433171-A-G
• rs3093319
• NM_181078.3:c.50-1176A>G

Variant summary

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

The NM_181078.3(IL21R):​c.50-1176A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,038 control chromosomes in the GnomAD database, including 11,074 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 (11074 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.50-1176A>G		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.116-1176A>G		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.50-1176A>G		intron	N/A	NP_068570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.50-1176A>G		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.50-1176A>G		intron	N/A	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.50-1176A>G		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54613 AN: 151920 Hom.: 11070 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.359 AC: 54621 AN: 152038 Hom.: 11074 Cov.: 32 AF XY: 0.358 AC XY: 26617 AN XY: 74324

African (AFR) AF: 0.174 AC: 7221 AN: 41472

American (AMR) AF: 0.337 AC: 5154 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1319 AN: 3466

East Asian (EAS) AF: 0.462 AC: 2390 AN: 5172

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4810

European-Finnish (FIN) AF: 0.454 AC: 4792 AN: 10554

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30587 AN: 67960

Other (OTH) AF: 0.363 AC: 766 AN: 2112

Alfa AF: 0.389 Hom.: 18849

Bravo AF: 0.343

Asia WGS AF: 0.361 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.46
PhyloP100		-0.58
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: rs3093319; hg19: chr16-27444492;