chr16-27431972-A-C

Variant names:

• chr16-27431972-A-C
• rs8057464
• NM_181078.3:c.49+1852A>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.49+1852A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,078 control chromosomes in the GnomAD database, including 50,790 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 0.82 (50790 hom., cov: 32)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.965 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.49+1852A>C		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.115+1852A>C		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.49+1852A>C		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.49+1852A>C		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.49+1852A>C		intron	N/A	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.49+1852A>C		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 123944 AN: 151960 Hom.: 50749 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.988

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.816 AC: 124046 AN: 152078 Hom.: 50790 Cov.: 32 AF XY: 0.821 AC XY: 61043 AN XY: 74332

African (AFR) AF: 0.833 AC: 34551 AN: 41456

American (AMR) AF: 0.784 AC: 11974 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3472

East Asian (EAS) AF: 0.988 AC: 5089 AN: 5152

South Asian (SAS) AF: 0.940 AC: 4531 AN: 4822

European-Finnish (FIN) AF: 0.849 AC: 8994 AN: 10590

Middle Eastern (MID) AF: 0.738 AC: 214 AN: 290

European-Non Finnish (NFE) AF: 0.791 AC: 53811 AN: 67992

Other (OTH) AF: 0.778 AC: 1642 AN: 2110

Alfa AF: 0.775 Hom.: 6333

Bravo AF: 0.809

Asia WGS AF: 0.940 AC: 3267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.13
PhyloP100		0.0
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: rs8057464; hg19: chr16-27443293;