chr16-27422997-C-T

Variant names:

• chr16-27422997-C-T
• rs11074861
• NM_181078.3:c.-16-7059C>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.-16-7059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,932 control chromosomes in the GnomAD database, including 10,036 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 (10036 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL21R	NM_181078.3	c.-16-7059C>T		intron_variant	Intron 1 of 8	ENST00000337929.8	NP_851564.1
IL21R	NM_181079.5	c.51-7059C>T		intron_variant	Intron 2 of 9		NP_851565.4
IL21R	XM_011545857.4	c.51-7059C>T		intron_variant	Intron 2 of 9		XP_011544159.1
IL21R	XM_017023257.3	c.-17+6718C>T		intron_variant	Intron 2 of 9		XP_016878746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.-16-7059C>T		intron_variant	Intron 1 of 8	1	NM_181078.3	ENSP00000338010.3
IL21R	ENST00000564089.5	c.-16-7059C>T		intron_variant	Intron 2 of 9	5		ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54228 AN: 151814 Hom.: 10031 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.357 AC: 54258 AN: 151932 Hom.: 10036 Cov.: 32 AF XY: 0.363 AC XY: 26972 AN XY: 74238

African (AFR) AF: 0.391 AC: 16183 AN: 41426

American (AMR) AF: 0.376 AC: 5733 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3472

East Asian (EAS) AF: 0.505 AC: 2605 AN: 5158

South Asian (SAS) AF: 0.493 AC: 2381 AN: 4826

European-Finnish (FIN) AF: 0.346 AC: 3640 AN: 10534

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

European-Non Finnish (NFE) AF: 0.319 AC: 21647 AN: 67956

Other (OTH) AF: 0.350 AC: 735 AN: 2098

Alfa AF: 0.327 Hom.: 1764

Bravo AF: 0.357

Asia WGS AF: 0.487 AC: 1694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		0.25
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: rs11074861; hg19: chr16-27434318;