chr16-27425462-T-C

Variant names:

• chr16-27425462-T-C
• rs8049804
• NM_181078.3:c.-16-4594T>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.-16-4594T>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 152,062 control chromosomes in the GnomAD database, including 10,167 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 (10167 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 = 0.525 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.-16-4594T>C		intron	N/A	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.51-4594T>C		intron	N/A	NP_851565.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.-16-4594T>C		intron	N/A	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.-16-4594T>C		intron	N/A	ENSP00000456707.1	Q9HBE5
	IL21R	ENST00000871346.1		c.-16-4594T>C		intron	N/A	ENSP00000541405.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54474 AN: 151944 Hom.: 10157 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.358 AC: 54513 AN: 152062 Hom.: 10167 Cov.: 32 AF XY: 0.364 AC XY: 27093 AN XY: 74334

African (AFR) AF: 0.391 AC: 16212 AN: 41452

American (AMR) AF: 0.374 AC: 5719 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3468

East Asian (EAS) AF: 0.542 AC: 2802 AN: 5174

South Asian (SAS) AF: 0.493 AC: 2378 AN: 4822

European-Finnish (FIN) AF: 0.343 AC: 3630 AN: 10574

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21693 AN: 67970

Other (OTH) AF: 0.353 AC: 745 AN: 2112

Alfa AF: 0.197 Hom.: 425

Bravo AF: 0.360

Asia WGS AF: 0.505 AC: 1758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.40
PhyloP100		-0.44
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: rs8049804; hg19: chr16-27436783;