22-17085121-T-A

Variant names:

• chr22-17085121-T-A
• rs577217331
• NM_014339.7:c.30T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_014339.7(IL17RA):​c.30T>A​(p.Ala10Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,403,778 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.849
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 22-17085121-T-A is Benign according to our data. Variant chr22-17085121-T-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 714588.
• BP7: Synonymous conserved (PhyloP=-0.849 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00185 (281/152170) while in subpopulation AFR AF = 0.00652 (271/41534). AF 95% confidence interval is 0.00589. There are 1 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.30T>A	p.Ala10Ala	synonymous	Exon 1 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.30T>A	p.Ala10Ala	synonymous	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.30T>A	p.Ala10Ala	synonymous	Exon 1 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.30T>A	p.Ala10Ala	synonymous	Exon 1 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.30T>A	p.Ala10Ala	synonymous	Exon 1 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152058 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000186 AC: 9 AN: 48482 AF XY: 0.000102

Gnomad AFR exome AF: 0.00940

Gnomad AMR exome AF: 0.000409

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.000173 AC: 217 AN: 1251608 Hom.: 1 Cov.: 59 AF XY: 0.000157 AC XY: 96 AN XY: 611376

African (AFR) AF: 0.00792 AC: 199 AN: 25142

American (AMR) AF: 0.000409 AC: 7 AN: 17120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19876

East Asian (EAS) AF: 0.00 AC: 0 AN: 27884

South Asian (SAS) AF: 0.00 AC: 0 AN: 62956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31542

Middle Eastern (MID) AF: 0.000203 AC: 1 AN: 4936

European-Non Finnish (NFE) AF: 9.89e-7 AC: 1 AN: 1010708

Other (OTH) AF: 0.000175 AC: 9 AN: 51444

GnomAD4 genome AF: 0.00185 AC: 281 AN: 152170 Hom.: 1 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74406

African (AFR) AF: 0.00652 AC: 271 AN: 41534

American (AMR) AF: 0.000457 AC: 7 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67964

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.00222

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Immunodeficiency 51 (2)
-	-	1	IL17RA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.6
DANN	Benign	0.63
PhyloP100		-0.85
PromoterAI		0.017	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	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: rs577217331; hg19: chr22-17566011;