rs179766

Variant names:

• chr16-27415473-C-A
• rs179766
• NM_181078.3:c.-17+12855C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-27415473-C-A
• chr16-27415473-C-G
• chr16-27415473-C-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.-17+12855C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 152,228 control chromosomes in the GnomAD database, including 46,749 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 0.78 (46749 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 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.-17+12855C>A		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.50+12253C>A		intron	N/A	NP_851565.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.-17+12855C>A		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000564089.5	TSL:5	c.-17+12253C>A		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117966 AN: 152110 Hom.: 46702 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.760

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.776 AC: 118071 AN: 152228 Hom.: 46749 Cov.: 32 AF XY: 0.782 AC XY: 58173 AN XY: 74408

African (AFR) AF: 0.924 AC: 38402 AN: 41570

American (AMR) AF: 0.746 AC: 11409 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5113 AN: 5186

South Asian (SAS) AF: 0.807 AC: 3893 AN: 4822

European-Finnish (FIN) AF: 0.760 AC: 8039 AN: 10578

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46552 AN: 67998

Other (OTH) AF: 0.717 AC: 1514 AN: 2112

Alfa AF: 0.700 Hom.: 4328

Bravo AF: 0.779

Asia WGS AF: 0.889 AC: 3091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.21
DANN	Benign	0.34
PhyloP100		-0.84
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: rs179766; hg19: chr16-27426794;