chr22-17085108-G-C

Variant names:

• chr22-17085108-G-C
• rs2061321130
• NM_014339.7:c.17G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014339.7(IL17RA):​c.17G>C​(p.Ser6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000822 in 1,216,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: IL17RA NM_014339.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.102
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 51

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043688595).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014339.7. 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
	IL17RA	NM_014339.7	MANE Select	c.17G>C	p.Ser6Thr	missense	Exon 1 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.17G>C	p.Ser6Thr	missense	Exon 1 of 12	NP_001276834.1	Q96F46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.17G>C	p.Ser6Thr	missense	Exon 1 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.17G>C	p.Ser6Thr	missense	Exon 1 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.17G>C	p.Ser6Thr	missense	Exon 1 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.22e-7 AC: 1 AN: 1216614 Hom.: 0 Cov.: 59 AF XY: 0.00000169 AC XY: 1 AN XY: 591134

African (AFR) AF: 0.00 AC: 0 AN: 24516

American (AMR) AF: 0.00 AC: 0 AN: 13192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17578

East Asian (EAS) AF: 0.00 AC: 0 AN: 27534

South Asian (SAS) AF: 0.00 AC: 0 AN: 55544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4862

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 993768

Other (OTH) AF: 0.00 AC: 0 AN: 49888

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.6
DANN	Benign	0.40
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.10
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.0080
Sift	Benign	0.76	T
Sift4G	Benign	0.71	T
Polyphen		0.033	B
Vest4		0.058
MutPred		0.14		Loss of glycosylation at S6 (P = 0.0641)
MVP		0.088
MPC		0.17
ClinPred		0.059	T
GERP RS		-0.34
PromoterAI		-0.031	Neutral
Varity_R		0.11
gMVP		0.39
Mutation Taster		=99/1	polymorphism

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: rs2061321130; hg19: chr22-17565998;