1-24121178-G-T

Position:

• chr1-24121178-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021258.4(IL22RA1):​c.1352C>A​(p.Thr451Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL22RA1 NM_021258.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.913

Genes affected

IL22RA1 (HGNC:13700): (interleukin 22 receptor subunit alpha 1) The protein encoded by this gene belongs to the class II cytokine receptor family, and has been shown to be a receptor for interleukin 22 (IL22). IL22 receptor is a protein complex that consists of this protein and interleukin 10 receptor, beta (IL10BR/CRFB4), a subunit also shared by the receptor complex for interleukin 10 (IL10). This gene and interleukin 28 receptor, alpha (IL28RA) form a cytokine receptor gene cluster in the chromosomal region 1p36. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10517496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL22RA1	NM_021258.4	c.1352C>A	p.Thr451Asn	missense_variant	7/7	ENST00000270800.2	NP_067081.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL22RA1	ENST00000270800.2	c.1352C>A	p.Thr451Asn	missense_variant	7/7	1	NM_021258.4	ENSP00000270800	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2021

The c.1352C>A (p.T451N) alteration is located in exon 7 (coding exon 7) of the IL22RA1 gene. This alteration results from a C to A substitution at nucleotide position 1352, causing the threonine (T) at amino acid position 451 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.080
Sift	Uncertain	0.015	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.72	P
Vest4		0.092
MutPred		0.089		Loss of glycosylation at T451 (P = 0.0587);
MVP		0.27
MPC		0.27
ClinPred		0.25	T
GERP RS		1.9
Varity_R		0.11
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1644117740; hg19: chr1-24447668;