16-27403057-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_181078.3(IL21R):c.-17+439T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 481,668 control chromosomes in the GnomAD database, including 186,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60863 hom., cov: 31)
  • Exomes 𝑓: 0.87 (125300 hom.)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.898

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-27403057-T-G is Benign according to our data. Variant chr16-27403057-T-G is described in ClinVar as [Benign]. Clinvar id is 1233904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL21R	NM_181078.3	c.-17+439T>G		intron_variant		ENST00000337929.8
IL21R	XM_011545857.4	c.-114T>G		5_prime_UTR_variant	2/10
IL21R	NM_181079.5	c.-91-23T>G		intron_variant
IL21R	XM_017023257.3	c.-147+439T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL21R	ENST00000337929.8	c.-17+439T>G		intron_variant		1	NM_181078.3	P1
IL21R	ENST00000564089.5	c.-157-23T>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135750 AN: 152060 Hom.: 60804 Cov.: 31

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.871 AC: 286981 AN: 329490 Hom.: 125300 Cov.: 3 AF XY: 0.871 AC XY: 157505 AN XY: 180874

Gnomad4 AFR exome AF: 0.965

Gnomad4 AMR exome AF: 0.908

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.804

Gnomad4 SAS exome AF: 0.878

Gnomad4 FIN exome AF: 0.902

Gnomad4 NFE exome AF: 0.863

Gnomad4 OTH exome AF: 0.867

GnomAD4 genome AF: 0.893 AC: 135866 AN: 152178 Hom.: 60863 Cov.: 31 AF XY: 0.895 AC XY: 66538 AN XY: 74384

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.899

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.886

Alfa AF: 0.882 Hom.: 11976

Bravo AF: 0.893

Asia WGS AF: 0.841 AC: 2925 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 97% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs6498021; hg19: chr16-27414378;