16-27429509-T-C

Variant names:

• chr16-27429509-T-C
• rs3093301
• NM_181078.3:c.-16-547T>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.-16-547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,054 control chromosomes in the GnomAD database, including 11,294 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 0.38 (11294 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 19 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 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.-16-547T>C		intron	N/A	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.51-547T>C		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.-16-547T>C		intron	N/A	NP_068570.1	Q9HBE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.-16-547T>C		intron	N/A	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000395754.4	TSL:1	c.-16-547T>C		intron	N/A	ENSP00000379103.4	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.-16-547T>C		intron	N/A	ENSP00000456707.1	Q9HBE5

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57685 AN: 151936 Hom.: 11286 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.380 AC: 57720 AN: 152054 Hom.: 11294 Cov.: 32 AF XY: 0.385 AC XY: 28620 AN XY: 74314

African (AFR) AF: 0.400 AC: 16598 AN: 41464

American (AMR) AF: 0.393 AC: 6002 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2798 AN: 5152

South Asian (SAS) AF: 0.524 AC: 2524 AN: 4816

European-Finnish (FIN) AF: 0.362 AC: 3829 AN: 10578

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23740 AN: 67980

Other (OTH) AF: 0.367 AC: 774 AN: 2108

Alfa AF: 0.301 Hom.: 1798

Bravo AF: 0.379

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.26
PhyloP100		-2.4
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: rs3093301; hg19: chr16-27440830;