chr16-27439438-A-G

Variant names:

• chr16-27439438-A-G
• rs3093349
• NM_181078.3:c.352+1751A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181078.3(IL21R):​c.352+1751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 151,880 control chromosomes in the GnomAD database, including 1,822 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (1822 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• 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 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 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.352+1751A>G		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.418+1751A>G		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.352+1751A>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.352+1751A>G		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.352+1751A>G		intron	N/A	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.352+1751A>G		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21011 AN: 151762 Hom.: 1812 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0523

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.139 AC: 21051 AN: 151880 Hom.: 1822 Cov.: 32 AF XY: 0.142 AC XY: 10564 AN XY: 74212

African (AFR) AF: 0.245 AC: 10122 AN: 41398

American (AMR) AF: 0.0882 AC: 1344 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3464

East Asian (EAS) AF: 0.101 AC: 524 AN: 5166

South Asian (SAS) AF: 0.0517 AC: 248 AN: 4798

European-Finnish (FIN) AF: 0.175 AC: 1845 AN: 10558

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0957 AC: 6505 AN: 67950

Other (OTH) AF: 0.117 AC: 247 AN: 2106

Alfa AF: 0.125 Hom.: 204

Bravo AF: 0.136

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		0.48
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: rs3093349; hg19: chr16-27450759;