NM_181078.3:c.507+246T>C

Variant names:

• chr16-27443362-T-C
• rs3093364
• NM_181078.3:c.507+246T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181078.3(IL21R):​c.507+246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,054 control chromosomes in the GnomAD database, including 1,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1745 hom., cov: 31)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.476
• 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

ENSG00000308281 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-27443362-T-C is Benign according to our data. Variant chr16-27443362-T-C is described in ClinVar as [Benign]. Clinvar id is 1236137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.507+246T>C		intron_variant	Intron 5 of 8	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.507+246T>C		intron_variant	Intron 5 of 8	1	NM_181078.3	ENSP00000338010.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19833 AN: 151936 Hom.: 1735 Cov.: 31

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0506

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.131 AC: 19876 AN: 152054 Hom.: 1745 Cov.: 31 AF XY: 0.134 AC XY: 9953 AN XY: 74328

African (AFR) AF: 0.239 AC: 9912 AN: 41446

American (AMR) AF: 0.0725 AC: 1108 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3468

East Asian (EAS) AF: 0.102 AC: 529 AN: 5170

South Asian (SAS) AF: 0.0501 AC: 241 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1830 AN: 10572

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5847 AN: 67988

Other (OTH) AF: 0.106 AC: 224 AN: 2108

Alfa AF: 0.0895 Hom.: 302

Bravo AF: 0.128

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.67
PhyloP100		-0.48
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: rs3093364; hg19: chr16-27454683;