chr22-17085111-C-T

Position:

chr22-17085111-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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. 13/20 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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0290

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 340562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17085111-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RA	NM_014339.7 linkuse as main transcript	c.20C>T	p.Pro7Leu	missense_variant	1/13	ENST00000319363.11
IL17RA	NM_001289905.2 linkuse as main transcript	c.20C>T	p.Pro7Leu	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11 linkuse as main transcript	c.20C>T	p.Pro7Leu	missense_variant	1/13	1	NM_014339.7	P2	Q96F46-1

Frequencies

GnomAD3 genomes

AF:

0.00379

AC:

577

AN:

152138

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00588

AC:

164

AN:

27870

Hom.:

AF XY:

0.00629

AC XY:

108

AN XY:

17162

show subpopulations

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 SAS exome

AF:

0.00340

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.:

Cov.:

AF XY:

0.00614

AC XY:

3648

AN XY:

594516

show subpopulations

Gnomad4 AFR exome

AF:

0.000690

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.00705

Gnomad4 OTH exome

AF:

0.00453

GnomAD4 genome

AF:

0.00378

AC:

576

AN:

152248

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00417

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00701

AC:

ExAC

AF:

0.00149

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Familial Candidiasis, Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Immunodeficiency 51

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

IL17RA-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 27, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.65

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

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.060

N;.

REVEL

Benign

0.0070

Sift

Benign

0.68

T;.

Sift4G

Benign

0.77

T;T

Polyphen

0.27

B;.

Vest4

0.076

MVP

0.12

MPC

0.19

ClinPred

0.0058

GERP RS

-0.092

Varity_R

0.022

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over