chr16-27441431-A-T

Variant names:

• chr16-27441431-A-T
• rs3093359
• NM_181078.3:c.353-1531A>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.353-1531A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,262 control chromosomes in the GnomAD database, including 1,758 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 0.13 (1758 hom., cov: 33)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.337
• 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

ENSG00000308281 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 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.353-1531A>T		intron	N/A	NP_851564.1
	IL21R	NM_181079.5		c.419-1531A>T		intron	N/A	NP_851565.4
	IL21R	NM_021798.4		c.353-1531A>T		intron	N/A	NP_068570.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL21R	ENST00000337929.8	TSL:1 MANE Select	c.353-1531A>T		intron	N/A	ENSP00000338010.3
	IL21R	ENST00000395754.4	TSL:1	c.353-1531A>T		intron	N/A	ENSP00000379103.4
	IL21R	ENST00000564089.5	TSL:5	c.353-1531A>T		intron	N/A	ENSP00000456707.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19955 AN: 152144 Hom.: 1748 Cov.: 33

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.131 AC: 19999 AN: 152262 Hom.: 1758 Cov.: 33 AF XY: 0.134 AC XY: 9998 AN XY: 74446

African (AFR) AF: 0.241 AC: 10021 AN: 41532

American (AMR) AF: 0.0729 AC: 1115 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3472

East Asian (EAS) AF: 0.102 AC: 530 AN: 5192

South Asian (SAS) AF: 0.0490 AC: 237 AN: 4832

European-Finnish (FIN) AF: 0.173 AC: 1833 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0861 AC: 5854 AN: 68014

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.115 Hom.: 172

Bravo AF: 0.128

Asia WGS AF: 0.109 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.82
PhyloP100		0.34
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: rs3093359; hg19: chr16-27452752;