Variant NM_181078.3:c.-17+400T>C 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+400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 433,330 control chromosomes in the GnomAD database, including 9,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2937 hom., cov: 32)

Exomes 𝑓: 0.20 ( 6607 hom. )

Consequence

IL21R
NM_181078.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.260

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-27403018-T-C is Benign according to our data. Variant chr16-27403018-T-C is described in ClinVar as [Benign]. Clinvar id is 1247564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3 link	c.-17+400T>C	intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1	Q9HBE5
IL21R	NM_181079.5 link	c.-91-62T>C	intron_variant	Intron 1 of 9		NP_851565.4	Q9HBE5
IL21R	XM_011545857.4 link	c.-127-26T>C	intron_variant	Intron 1 of 9		XP_011544159.1
IL21R	XM_017023257.3 link	c.-147+400T>C	intron_variant	Intron 1 of 9		XP_016878746.1	Q9HBE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8 link	c.-17+400T>C		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3		Q9HBE5
IL21R	ENST00000564089.5 link	c.-157-62T>C		intron_variant	Intron 1 of 9	5		ENSP00000456707.1		Q9HBE5

Frequencies

GnomAD3 genomes

AF:

0.172

AC:

26086

AN:

152090

Hom.:

2937

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.0139

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.252

Gnomad OTH

AF:

0.226

GnomAD4 exome

AF:

0.199

AC:

56064

AN:

281122

Hom.:

6607

AF XY:

0.196

AC XY:

30000

AN XY:

152806

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.133

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.250

Gnomad4 OTH exome

AF:

0.218

GnomAD4 genome

AF:

0.171

AC:

26080

AN:

152208

Hom.:

2937

Cov.:

AF XY:

0.165

AC XY:

12281

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0511

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.252

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.221

Hom.:

2045

Bravo

AF:

0.167

Asia WGS

AF:

0.0840

AC:

292

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 12700598, 17015683) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Increased circulating IgE concentration

Benign:1

Apr 01, 2003

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

DANN

Benign

0.68

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