rs721930

Variant names:

• chr22-17104918-G-C
• rs721930
• NM_014339.7:c.931+108G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014339.7(IL17RA):​c.931+108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,054,154 control chromosomes in the GnomAD database, including 19,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2248 hom., cov: 32)
  • Exomes 𝑓: 0.19 (17540 hom.)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 9 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.931+108G>C		intron_variant	Intron 9 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.931+108G>C		intron_variant	Intron 9 of 11		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.931+108G>C		intron_variant	Intron 9 of 12	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.931+108G>C		intron_variant	Intron 9 of 11	5		ENSP00000479970.1
IL17RA	ENST00000694951.1	n.*150G>C		downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23859 AN: 152044 Hom.: 2250 Cov.: 32

Gnomad AFR AF: 0.0570

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.190 AC: 171341 AN: 901990 Hom.: 17540 AF XY: 0.192 AC XY: 89313 AN XY: 465930

African (AFR) AF: 0.0502 AC: 1127 AN: 22462

American (AMR) AF: 0.150 AC: 5456 AN: 36262

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 4766 AN: 22052

East Asian (EAS) AF: 0.326 AC: 11297 AN: 34662

South Asian (SAS) AF: 0.201 AC: 14239 AN: 70728

European-Finnish (FIN) AF: 0.187 AC: 8871 AN: 47366

Middle Eastern (MID) AF: 0.171 AC: 811 AN: 4732

European-Non Finnish (NFE) AF: 0.188 AC: 116884 AN: 621814

Other (OTH) AF: 0.188 AC: 7890 AN: 41912

GnomAD4 genome AF: 0.157 AC: 23856 AN: 152164 Hom.: 2248 Cov.: 32 AF XY: 0.159 AC XY: 11792 AN XY: 74376

African (AFR) AF: 0.0569 AC: 2361 AN: 41524

American (AMR) AF: 0.157 AC: 2397 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.306 AC: 1580 AN: 5170

South Asian (SAS) AF: 0.199 AC: 962 AN: 4824

European-Finnish (FIN) AF: 0.191 AC: 2022 AN: 10588

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13145 AN: 67988

Other (OTH) AF: 0.159 AC: 335 AN: 2108

Alfa AF: 0.170 Hom.: 354

Bravo AF: 0.152

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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: rs721930; hg19: chr22-17585808; COSMIC: COSV60053529; COSMIC: COSV60053529;