rs767388612

Positions:

• chr22-17103563-C-G
• chr22-17103563-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.832C>G​(p.Arg278Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R278H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: IL17RA NM_014339.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.917

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]

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=0.106475055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.832C>G	p.Arg278Gly	missense_variant	8/13	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.832C>G	p.Arg278Gly	missense_variant	8/12		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.832C>G	p.Arg278Gly	missense_variant	8/13	1	NM_014339.7	ENSP00000320936	P2
IL17RA	ENST00000612619.2	c.832C>G	p.Arg278Gly	missense_variant	8/12	5		ENSP00000479970	A2
IL17RA	ENST00000694951.1	n.790C>G		non_coding_transcript_exon_variant	6/7
IL17RA	ENST00000694950.1	c.*337C>G		3_prime_UTR_variant, NMD_transcript_variant	7/7			ENSP00000511613

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000806 AC: 2 AN: 248234 Hom.: 0 AF XY: 0.00000745 AC XY: 1 AN XY: 134298

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460412 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726386

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.095
Sift	Benign	0.14	T;.
Sift4G	Benign	0.19	T;T
Polyphen		0.11	B;.
Vest4		0.26
MutPred		0.43		Loss of MoRF binding (P = 0.0084);Loss of MoRF binding (P = 0.0084);
MVP		0.31
MPC		0.26
ClinPred		0.097	T
GERP RS		4.6
Varity_R		0.43
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs767388612; hg19: chr22-17584453;