rs3093341

Variant names:

• chr16-27437080-A-G
• rs3093341
• NM_181078.3:c.153-408A>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.153-408A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,074 control chromosomes in the GnomAD database, including 2,142 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 0.15 (2142 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• 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 (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.153-408A>G		intron_variant	Intron 3 of 8	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.153-408A>G		intron_variant	Intron 3 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.153-408A>G		intron_variant	Intron 3 of 8	1		ENSP00000379103.4
IL21R	ENST00000564089.5	c.153-408A>G		intron_variant	Intron 4 of 9	5		ENSP00000456707.1
IL21R	ENST00000697146.1	n.153-408A>G		intron_variant	Intron 2 of 6			ENSP00000513135.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22228 AN: 151956 Hom.: 2130 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0475

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0529

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.146 AC: 22277 AN: 152074 Hom.: 2142 Cov.: 32 AF XY: 0.150 AC XY: 11190 AN XY: 74354

African (AFR) AF: 0.271 AC: 11234 AN: 41450

American (AMR) AF: 0.0901 AC: 1378 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0475 AC: 165 AN: 3472

East Asian (EAS) AF: 0.103 AC: 533 AN: 5170

South Asian (SAS) AF: 0.0526 AC: 253 AN: 4812

European-Finnish (FIN) AF: 0.176 AC: 1857 AN: 10580

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0961 AC: 6533 AN: 67976

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.117 Hom.: 2404

Bravo AF: 0.145

Asia WGS AF: 0.119 AC: 412 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	1.2
DANN	Benign	0.83
PhyloP100		-0.29
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: rs3093341; hg19: chr16-27448401;