Variant chr16-27403057-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.898

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein
IL21R	NM_181078.3 linkuse as main transcript	c.-17+439T>G	intron_variant		ENST00000337929.8	NP_851564.1
IL21R	XM_011545857.4 linkuse as main transcript	c.-114T>G	5_prime_UTR_variant	2/10		XP_011544159.1
IL21R	NM_181079.5 linkuse as main transcript	c.-91-23T>G	intron_variant			NP_851565.4
IL21R	XM_017023257.3 linkuse as main transcript	c.-147+439T>G	intron_variant			XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 linkuse as main transcript	c.-17+439T>G		intron_variant		1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000564089.5 linkuse as main transcript	c.-157-23T>G		intron_variant		5		ENSP00000456707	P1

Frequencies

GnomAD3 genomes

AF:

0.893

AC:

135750

AN:

152060

Hom.:

60804

Cov.:

show subpopulations

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.:

AF XY:

0.871

AC XY:

157505

AN XY:

180874

show subpopulations

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.:

AF XY:

0.895

AC XY:

66538

AN XY:

74384

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

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. -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over