16-27429962-A-G

Variant names:

• chr16-27429962-A-G
• rs179760
• NM_181078.3:c.-16-94A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):​c.-16-94A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,047,690 control chromosomes in the GnomAD database, including 333,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47785 hom., cov: 29)
  • Exomes 𝑓: 0.80 (286145 hom.)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.924
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-27429962-A-G is Benign according to our data. Variant chr16-27429962-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.-16-94A>G		intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.-16-94A>G		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000395754.4	c.-16-94A>G		intron_variant	Intron 1 of 8	1		ENSP00000379103.4
IL21R	ENST00000564089.5	c.-16-94A>G		intron_variant	Intron 2 of 9	5		ENSP00000456707.1
IL21R	ENST00000697146.1	n.-110A>G		upstream_gene_variant				ENSP00000513135.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120073 AN: 151852 Hom.: 47743 Cov.: 29

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.745

GnomAD4 exome AF: 0.796 AC: 713142 AN: 895720 Hom.: 286145 AF XY: 0.801 AC XY: 364650 AN XY: 455432

African (AFR) AF: 0.791 AC: 17284 AN: 21854

American (AMR) AF: 0.764 AC: 22714 AN: 29744

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 13486 AN: 20230

East Asian (EAS) AF: 0.996 AC: 32700 AN: 32834

South Asian (SAS) AF: 0.929 AC: 61272 AN: 65954

European-Finnish (FIN) AF: 0.834 AC: 28901 AN: 34656

Middle Eastern (MID) AF: 0.757 AC: 3519 AN: 4650

European-Non Finnish (NFE) AF: 0.777 AC: 501093 AN: 644590

Other (OTH) AF: 0.781 AC: 32173 AN: 41208

GnomAD4 genome AF: 0.791 AC: 120173 AN: 151970 Hom.: 47785 Cov.: 29 AF XY: 0.799 AC XY: 59367 AN XY: 74292

African (AFR) AF: 0.788 AC: 32644 AN: 41440

American (AMR) AF: 0.747 AC: 11406 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2326 AN: 3468

East Asian (EAS) AF: 0.988 AC: 5080 AN: 5140

South Asian (SAS) AF: 0.941 AC: 4536 AN: 4820

European-Finnish (FIN) AF: 0.856 AC: 9068 AN: 10598

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.774 AC: 52542 AN: 67918

Other (OTH) AF: 0.746 AC: 1574 AN: 2110

Alfa AF: 0.772 Hom.: 135237

Bravo AF: 0.781

Asia WGS AF: 0.943 AC: 3277 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 94% of patients studied by a panel of primary immunodeficiencies. Number of patients: 83. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.030
DANN	Benign	0.25
PhyloP100		-0.92
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: rs179760; hg19: chr16-27441283;