rs56002407

Variant names:

• chr16-27449133-G-A
• rs56002407
• NM_181078.3:c.1467G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_181078.3(IL21R):​c.1467G>A​(p.Thr489Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,440 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (3 hom.)
• Consequence: IL21R NM_181078.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.623
• Publications: 1 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-AS1 (HGNC:27551): (IL21R antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-27449133-G-A is Benign according to our data. Variant chr16-27449133-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 540995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.623 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.1467G>A	p.Thr489Thr	synonymous	Exon 9 of 9	NP_851564.1
	IL21R	NM_181079.5		c.1533G>A	p.Thr511Thr	synonymous	Exon 10 of 10	NP_851565.4
	IL21R	NM_021798.4		c.1467G>A	p.Thr489Thr	synonymous	Exon 9 of 9	NP_068570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.1467G>A	p.Thr489Thr	synonymous	Exon 9 of 9	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.1467G>A	p.Thr489Thr	synonymous	Exon 9 of 9	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.1467G>A	p.Thr489Thr	synonymous	Exon 10 of 10	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00103 AC: 258 AN: 250062 AF XY: 0.00105

Gnomad AFR exome AF: 0.00257

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.000983

GnomAD4 exome AF: 0.00202 AC: 2949 AN: 1461102 Hom.: 3 Cov.: 31 AF XY: 0.00192 AC XY: 1392 AN XY: 726872

African (AFR) AF: 0.00236 AC: 79 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.000209 AC: 11 AN: 52648

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00248 AC: 2756 AN: 1112002

Other (OTH) AF: 0.00137 AC: 83 AN: 60388

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152338 Hom.: 0 Cov.: 33 AF XY: 0.00136 AC XY: 101 AN XY: 74488

African (AFR) AF: 0.00190 AC: 79 AN: 41584

American (AMR) AF: 0.000588 AC: 9 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00228 AC: 155 AN: 68018

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00177 Hom.: 0

Bravo AF: 0.00170

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cryptosporidiosis-chronic cholangitis-liver disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.6
DANN	Benign	0.84
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism

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: rs56002407; hg19: chr16-27460454;