rs145378071

Positions:

• chr22-17100358-C-G
• chr22-17100358-C-T

Variant summary

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

The NM_014339.7(IL17RA):​c.427C>G​(p.Arg143Gly) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RA NM_014339.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.635

Genes affected

IL17RA (HGNC:5985): (interleukin 17 receptor A) Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

IL17RA (HGNC:):

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=0.17620677).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.427C>G	p.Arg143Gly	missense_variant	5/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.427C>G	p.Arg143Gly	missense_variant	5/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.427C>G	p.Arg143Gly	missense_variant	5/13	1	NM_014339.7	ENSP00000320936.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251458 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.5	N;.
REVEL	Benign	0.12
Sift	Benign	0.21	T;.
Sift4G	Benign	0.10	T;T
Polyphen		0.89	P;.
Vest4		0.40
MutPred		0.40		Loss of MoRF binding (P = 0.0414);Loss of MoRF binding (P = 0.0414);
MVP		0.15
MPC		0.32
ClinPred		0.30	T
GERP RS		1.5
Varity_R		0.32
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs145378071; hg19: chr22-17581248;