16-27423212-G-C

Variant names:

• chr16-27423212-G-C
• rs7199138
• NM_181078.3:c.-16-6844G>C

Variant summary

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

The NM_181078.3(IL21R):​c.-16-6844G>C 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 150,298 control chromosomes in the GnomAD database, including 10,042 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 (10042 hom., cov: 31)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 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.-16-6844G>C		intron	N/A	NP_851564.1	Q9HBE5
	IL21R	NM_181079.5		c.51-6844G>C		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.-16-6844G>C		intron	N/A	ENSP00000338010.3	Q9HBE5
	IL21R	ENST00000564089.5	TSL:5	c.-16-6844G>C		intron	N/A	ENSP00000456707.1	Q9HBE5
	IL21R	ENST00000871346.1		c.-16-6844G>C		intron	N/A	ENSP00000541405.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54153 AN: 150192 Hom.: 10035 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.319

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: 54191 AN: 150298 Hom.: 10042 Cov.: 31 AF XY: 0.367 AC XY: 26949 AN XY: 73468

African (AFR) AF: 0.399 AC: 16142 AN: 40444

American (AMR) AF: 0.379 AC: 5748 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 955 AN: 3468

East Asian (EAS) AF: 0.508 AC: 2618 AN: 5150

South Asian (SAS) AF: 0.497 AC: 2376 AN: 4776

European-Finnish (FIN) AF: 0.353 AC: 3607 AN: 10230

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21625 AN: 67762

Other (OTH) AF: 0.353 AC: 742 AN: 2100

Alfa AF: 0.323 Hom.: 1041

Bravo AF: 0.357

Asia WGS AF: 0.486 AC: 1692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.37
PhyloP100		0.010
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: rs7199138; hg19: chr16-27434533;