16-27430090-G-A

Position:

chr16-27430090-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_181078.3(IL21R):c.19G>A(p.Ala7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,605,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

IL21R
NM_181078.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.115

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004985571).

BP6

Variant 16-27430090-G-A is Benign according to our data. Variant chr16-27430090-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 540994.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-27430090-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	2/9	ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IL21R	ENST00000337929.8 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	2/9	1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	2/9	1		ENSP00000379103	P1
IL21R	ENST00000564089.5 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant	3/10	5		ENSP00000456707	P1
IL21R	ENST00000697146.1 linkuse as main transcript	c.19G>A	p.Ala7Thr	missense_variant, NMD_transcript_variant	1/7			ENSP00000513135

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000196

AC:

AN:

239286

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

130862

show subpopulations

Gnomad AFR exome

AF:

0.00259

Gnomad AMR exome

AF:

0.0000875

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000557

AC:

AN:

1453076

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

723298

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000545

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000555

ESP6500AA

AF:

0.00296

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000289

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Cryptosporidiosis-chronic cholangitis-liver disease syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 09, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

3.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

T;T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.50

.;.;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.69

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.096

T;T;T

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.053

B;B;B

Vest4

0.15

MVP

0.59

MPC

0.27

ClinPred

0.0049

GERP RS

0.70

Varity_R

0.033

gMVP

0.72

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