16-27432182-C-T

Variant names:

• chr16-27432182-C-T
• rs3093310
• NM_181078.3:c.49+2062C>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.49+2062C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,154 control chromosomes in the GnomAD database, including 11,389 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 (11389 hom., cov: 33)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.49+2062C>T		intron_variant	Intron 2 of 8	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.49+2062C>T		intron_variant	Intron 2 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.49+2062C>T		intron_variant	Intron 2 of 8	1		ENSP00000379103.4
IL21R	ENST00000564089.5	c.49+2062C>T		intron_variant	Intron 3 of 9	5		ENSP00000456707.1
IL21R	ENST00000697146.1	n.49+2062C>T		intron_variant	Intron 1 of 6			ENSP00000513135.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57178 AN: 152036 Hom.: 11380 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.376 AC: 57220 AN: 152154 Hom.: 11389 Cov.: 33 AF XY: 0.376 AC XY: 28003 AN XY: 74378

African (AFR) AF: 0.255 AC: 10596 AN: 41542

American (AMR) AF: 0.335 AC: 5128 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.466 AC: 2403 AN: 5160

South Asian (SAS) AF: 0.390 AC: 1881 AN: 4828

European-Finnish (FIN) AF: 0.457 AC: 4825 AN: 10566

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29690 AN: 67974

Other (OTH) AF: 0.378 AC: 800 AN: 2114

Alfa AF: 0.401 Hom.: 1893

Bravo AF: 0.362

Asia WGS AF: 0.384 AC: 1339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-2.5
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: rs3093310; hg19: chr16-27443503;