chr16-27421414-C-T

Variant names:

• chr16-27421414-C-T
• rs2040790
• NM_181078.3:c.-16-8642C>T

Variant summary

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

The NM_181078.3(IL21R):​c.-16-8642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 148,370 control chromosomes in the GnomAD database, including 9,965 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 0.36 (9965 hom., cov: 29)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 6 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	NM_181078.3	MANE Select	c.-16-8642C>T		intron	N/A	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.51-8642C>T		intron	N/A	NP_851565.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.-16-8642C>T		intron	N/A	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.-16-8642C>T		intron	N/A	ENSP00000456707.1	Q9HBE5
	IL21R	ENST00000871346.1		c.-17+5135C>T		intron	N/A	ENSP00000541405.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 53579 AN: 148280 Hom.: 9957 Cov.: 29

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.361 AC: 53617 AN: 148370 Hom.: 9965 Cov.: 29 AF XY: 0.368 AC XY: 26522 AN XY: 72008

African (AFR) AF: 0.398 AC: 16085 AN: 40460

American (AMR) AF: 0.378 AC: 5617 AN: 14862

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 952 AN: 3442

East Asian (EAS) AF: 0.513 AC: 2588 AN: 5040

South Asian (SAS) AF: 0.503 AC: 2364 AN: 4704

European-Finnish (FIN) AF: 0.362 AC: 3366 AN: 9308

Middle Eastern (MID) AF: 0.350 AC: 100 AN: 286

European-Non Finnish (NFE) AF: 0.320 AC: 21541 AN: 67306

Other (OTH) AF: 0.353 AC: 726 AN: 2058

Alfa AF: 0.342 Hom.: 6295

Bravo AF: 0.358

Asia WGS AF: 0.485 AC: 1683 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.62
PhyloP100		-0.072
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: rs2040790; hg19: chr16-27432735;