NM_014339.7:c.20C>T

Variant names:

• chr22-17085111-C-T
• rs143652002
• NM_014339.7:c.20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_014339.7(IL17RA):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00591 in 1,374,558 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (29 hom.)
• Consequence: IL17RA NM_014339.7 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0290
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030026138).
• BP6: Variant 22-17085111-C-T is Benign according to our data. Variant chr22-17085111-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 340562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00378 (576/152248) while in subpopulation NFE AF = 0.00606 (412/67990). AF 95% confidence interval is 0.00558. There are 3 homozygotes in GnomAd4. There are 266 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AD,AR gene

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.20C>T	p.Pro7Leu	missense	Exon 1 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.20C>T	p.Pro7Leu	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.20C>T	p.Pro7Leu	missense	Exon 1 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.20C>T	p.Pro7Leu	missense	Exon 1 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.20C>T	p.Pro7Leu	missense	Exon 1 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00379 AC: 577 AN: 152138 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00606

Gnomad OTH AF: 0.00525

GnomAD2 exomes AF: 0.00588 AC: 164 AN: 27870 AF XY: 0.00629

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00639

Gnomad NFE exome AF: 0.00968

Gnomad OTH exome AF: 0.00605

GnomAD4 exome AF: 0.00618 AC: 7554 AN: 1222310 Hom.: 29 Cov.: 59 AF XY: 0.00614 AC XY: 3648 AN XY: 594516

African (AFR) AF: 0.000690 AC: 17 AN: 24648

American (AMR) AF: 0.00367 AC: 51 AN: 13914

Ashkenazi Jewish (ASJ) AF: 0.00128 AC: 23 AN: 17964

East Asian (EAS) AF: 0.00 AC: 0 AN: 27586

South Asian (SAS) AF: 0.00245 AC: 139 AN: 56644

European-Finnish (FIN) AF: 0.00183 AC: 55 AN: 30062

Middle Eastern (MID) AF: 0.00433 AC: 21 AN: 4854

European-Non Finnish (NFE) AF: 0.00705 AC: 7021 AN: 996514

Other (OTH) AF: 0.00453 AC: 227 AN: 50124

GnomAD4 genome AF: 0.00378 AC: 576 AN: 152248 Hom.: 3 Cov.: 33 AF XY: 0.00357 AC XY: 266 AN XY: 74446

African (AFR) AF: 0.00101 AC: 42 AN: 41564

American (AMR) AF: 0.00484 AC: 74 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5156

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10620

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00606 AC: 412 AN: 67990

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

Alfa AF: 0.00297 Hom.: 0

Bravo AF: 0.00417

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00701 AC: 27

ExAC AF: 0.00149 AC: 65

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Familial Candidiasis, Recessive (1)
-	-	1	IL17RA-related disorder (1)
-	-	1	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.8
DANN	Benign	0.80
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.59	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.029
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.0070
Sift	Benign	0.68	T
Sift4G	Benign	0.77	T
Polyphen		0.27	B
Vest4		0.076
MVP		0.12
MPC		0.19
ClinPred		0.0058	T
GERP RS		-0.092
PromoterAI		0.014	Neutral
Varity_R		0.022
gMVP		0.46
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: rs143652002; hg19: chr22-17566001; COSMIC: COSV60055527; COSMIC: COSV60055527;