rs3093408

Variant names:

• chr16-27449115-C-T
• rs3093408
• NM_181078.3:c.1449C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-27449115-C-T
• chr16-27449115-C-A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_181078.3(IL21R):​c.1449C>T​(p.Ala483Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,613,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: IL21R NM_181078.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 16-27449115-C-T is Benign according to our data. Variant chr16-27449115-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 540999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.

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.1449C>T	p.Ala483Ala	synonymous	Exon 9 of 9	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.1515C>T	p.Ala505Ala	synonymous	Exon 10 of 10	NP_851565.4
	IL21R	NM_021798.4		c.1449C>T	p.Ala483Ala	synonymous	Exon 9 of 9	NP_068570.1	Q9HBE5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.1449C>T	p.Ala483Ala	synonymous	Exon 9 of 9	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000395754.4	TSL:1	c.1449C>T	p.Ala483Ala	synonymous	Exon 9 of 9	ENSP00000379103.4	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.1449C>T	p.Ala483Ala	synonymous	Exon 10 of 10	ENSP00000456707.1	Q9HBE5

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152172 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000180 AC: 45 AN: 250110 AF XY: 0.000207

Gnomad AFR exome AF: 0.0000624

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000346

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000231 AC: 337 AN: 1461182 Hom.: 0 Cov.: 31 AF XY: 0.000226 AC XY: 164 AN XY: 726940

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52766

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

European-Non Finnish (NFE) AF: 0.000291 AC: 324 AN: 1111980

Other (OTH) AF: 0.0000994 AC: 6 AN: 60382

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152290 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74460

African (AFR) AF: 0.0000481 AC: 2 AN: 41564

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000339 Hom.: 0

Bravo AF: 0.000159

EpiCase AF: 0.000545

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cryptosporidiosis-chronic cholangitis-liver disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.26
DANN	Benign	0.75
PhyloP100		-1.6

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: rs3093408; hg19: chr16-27460436; COSMIC: COSV100560498; COSMIC: COSV100560498;