rs3093379

Variant names:

• chr16-27446754-G-A
• rs3093379
• NM_181078.3:c.867+666G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27446754-G-A
• chr16-27446754-G-T

Variant summary

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

The NM_181078.3(IL21R):​c.867+666G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,810 control chromosomes in the GnomAD database, including 9,551 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 0.34 (9551 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.890
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.867+666G>A		intron_variant	Intron 8 of 8	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.867+666G>A		intron_variant	Intron 8 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.867+666G>A		intron_variant	Intron 8 of 8	1		ENSP00000379103.4
IL21R	ENST00000564089.5	c.867+666G>A		intron_variant	Intron 9 of 9	5		ENSP00000456707.1
IL21R	ENST00000564583.1	n.425+666G>A		intron_variant	Intron 4 of 4	4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52154 AN: 151692 Hom.: 9516 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.324

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

GnomAD4 genome AF: 0.344 AC: 52224 AN: 151810 Hom.: 9551 Cov.: 32 AF XY: 0.344 AC XY: 25518 AN XY: 74172

African (AFR) AF: 0.480 AC: 19875 AN: 41364

American (AMR) AF: 0.294 AC: 4490 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.106 AC: 551 AN: 5178

South Asian (SAS) AF: 0.123 AC: 590 AN: 4798

European-Finnish (FIN) AF: 0.343 AC: 3612 AN: 10538

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21182 AN: 67884

Other (OTH) AF: 0.322 AC: 681 AN: 2114

Alfa AF: 0.335 Hom.: 1286

Bravo AF: 0.346

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.44
PhyloP100		-0.89
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: rs3093379; hg19: chr16-27458075;