16-27434039-G-C

Position:

• chr16-27434039-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_181078.3(IL21R):​c.50-308G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,104 control chromosomes in the GnomAD database, including 5,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (5458 hom., cov: 31)
• Consequence: IL21R NM_181078.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-27434039-G-C is Benign according to our data. Variant chr16-27434039-G-C is described in ClinVar as [Benign]. Clinvar id is 1242635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL21R	NM_181078.3	c.50-308G>C		intron_variant		ENST00000337929.8	NP_851564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL21R	ENST00000337929.8	c.50-308G>C		intron_variant		1	NM_181078.3	ENSP00000338010	P1
IL21R	ENST00000395754.4	c.50-308G>C		intron_variant		1		ENSP00000379103	P1
IL21R	ENST00000564089.5	c.50-308G>C		intron_variant		5		ENSP00000456707	P1
IL21R	ENST00000697146.1	c.50-308G>C		intron_variant, NMD_transcript_variant				ENSP00000513135

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35328 AN: 151986 Hom.: 5459 Cov.: 31

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.232 AC: 35318 AN: 152104 Hom.: 5458 Cov.: 31 AF XY: 0.236 AC XY: 17539 AN XY: 74354

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.252

Alfa AF: 0.137 Hom.: 291

Bravo AF: 0.232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs3093322; hg19: chr16-27445360;