22-17085108-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.102

Publications

0 publications found

Variant links:

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

IL17RA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.17G>C	p.Ser6Thr	missense_variant	Exon 1 of 13	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.17G>C	p.Ser6Thr	missense_variant	Exon 1 of 12		NP_001276834.1	Q96F46-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.17G>C	p.Ser6Thr	missense_variant	Exon 1 of 13	1	NM_014339.7	ENSP00000320936.6		Q96F46-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.22e-7

AC:

AN:

1216614

Hom.:

Cov.:

AF XY:

0.00000169

AC XY:

AN XY:

591134

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24516

American (AMR)

AF:

0.00

AC:

AN:

13192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17578

East Asian (EAS)

AF:

0.00

AC:

AN:

27534

South Asian (SAS)

AF:

0.00

AC:

AN:

55544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4862

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

993768

Other (OTH)

AF:

0.00

AC:

AN:

49888

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.17G>C (p.S6T) alteration is located in exon 1 (coding exon 1) of the IL17RA gene. This alteration results from a G to C substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.6

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

PhyloP100

-0.10

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.13

N;.

REVEL

Benign

0.0080

Sift

Benign

0.76

T;.

Sift4G

Benign

0.71

T;T

Polyphen

0.033

B;.

Vest4

0.058

MutPred

0.14

Loss of glycosylation at S6 (P = 0.0641);Loss of glycosylation at S6 (P = 0.0641);

MVP

0.088

MPC

0.17

ClinPred

0.059

GERP RS

-0.34

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.11

gMVP

0.39

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over