chr22-17085108-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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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