NM_181078.3:c.786-170T>G

Variant names:

• chr16-27445837-T-G
• rs3093375
• NM_181078.3:c.786-170T>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.786-170T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,874 control chromosomes in the GnomAD database, including 9,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.34 (9558 hom., cov: 31)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.590
• Publications: 2 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=-0.88).
• BP6: Variant 16-27445837-T-G is Benign according to our data. Variant chr16-27445837-T-G is described in ClinVar as Benign. ClinVar VariationId is 1251522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.786-170T>G		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.852-170T>G		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.786-170T>G		intron	N/A	NP_068570.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.786-170T>G		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.786-170T>G		intron	N/A	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.786-170T>G		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52198 AN: 151756 Hom.: 9523 Cov.: 31

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 52269 AN: 151874 Hom.: 9558 Cov.: 31 AF XY: 0.344 AC XY: 25539 AN XY: 74222

African (AFR) AF: 0.480 AC: 19881 AN: 41382

American (AMR) AF: 0.294 AC: 4498 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3472

East Asian (EAS) AF: 0.107 AC: 551 AN: 5166

South Asian (SAS) AF: 0.124 AC: 594 AN: 4802

European-Finnish (FIN) AF: 0.342 AC: 3605 AN: 10552

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.312 AC: 21221 AN: 67914

Other (OTH) AF: 0.321 AC: 677 AN: 2106

Alfa AF: 0.352 Hom.: 1528

Bravo AF: 0.346

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.1
DANN	Benign	0.60
PhyloP100		0.59
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: rs3093375; hg19: chr16-27457158; COSMIC: COSV61971396; COSMIC: COSV61971396;