NM_014339.7:c.1046-642G>A

Variant names:

• chr22-17107085-G-A
• rs6518661
• NM_014339.7:c.1046-642G>A

Variant summary

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

The NM_014339.7(IL17RA):​c.1046-642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 152,070 control chromosomes in the GnomAD database, including 9,841 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 0.35 (9841 hom., cov: 32)
• Consequence: IL17RA NM_014339.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 19 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7	c.1046-642G>A		intron_variant	Intron 11 of 12	ENST00000319363.11	NP_055154.3
IL17RA	NM_001289905.2	c.944-642G>A		intron_variant	Intron 10 of 11		NP_001276834.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11	c.1046-642G>A		intron_variant	Intron 11 of 12	1	NM_014339.7	ENSP00000320936.6
IL17RA	ENST00000612619.2	c.944-642G>A		intron_variant	Intron 10 of 11	5		ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53190 AN: 151952 Hom.: 9839 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.350 AC: 53216 AN: 152070 Hom.: 9841 Cov.: 32 AF XY: 0.344 AC XY: 25594 AN XY: 74358

African (AFR) AF: 0.420 AC: 17382 AN: 41426

American (AMR) AF: 0.271 AC: 4144 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3470

East Asian (EAS) AF: 0.0590 AC: 306 AN: 5184

South Asian (SAS) AF: 0.284 AC: 1371 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3429 AN: 10582

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23843 AN: 67972

Other (OTH) AF: 0.363 AC: 766 AN: 2110

Alfa AF: 0.349 Hom.: 15813

Bravo AF: 0.347

Asia WGS AF: 0.204 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.66
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: rs6518661; hg19: chr22-17587975;