22-17105581-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014339.7(IL17RA):c.932-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,610,648 control chromosomes in the GnomAD database, including 510,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 51244 hom., cov: 33)

Exomes 𝑓: 0.79 ( 459740 hom. )

Consequence

IL17RA
NM_014339.7 intron

Scores

Splicing: ADA: 0.00001350

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: -0.116

Publications

26 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 22-17105581-C-T is Benign according to our data. Variant chr22-17105581-C-T is described in ClinVar as Benign. ClinVar VariationId is 340585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RA	NM_014339.7 link	c.932-10C>T		intron_variant	Intron 9 of 12	ENST00000319363.11	NP_055154.3	Q96F46-1
IL17RA	NM_001289905.2 link	c.932-10C>T		intron_variant	Intron 9 of 11		NP_001276834.1	Q96F46-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RA	ENST00000319363.11 link	c.932-10C>T		intron_variant	Intron 9 of 12	1	NM_014339.7	ENSP00000320936.6		Q96F46-1
IL17RA	ENST00000612619.2 link	c.932-10C>T		intron_variant	Intron 9 of 11	5		ENSP00000479970.1		Q96F46-2

Frequencies

GnomAD3 genomes

AF:

0.819

AC:

124554

AN:

152122

Hom.:

51177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.797

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.805

Gnomad EAS

AF:

0.823

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.842

Gnomad NFE

AF:

0.785

Gnomad OTH

AF:

0.828

GnomAD2 exomes

AF:

0.812

AC:

204298

AN:

251466

AF XY:

0.808

show subpopulations

Gnomad AFR exome

AF:

0.882

Gnomad AMR exome

AF:

0.894

Gnomad ASJ exome

AF:

0.819

Gnomad EAS exome

AF:

0.820

Gnomad FIN exome

AF:

0.744

Gnomad NFE exome

AF:

0.786

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.793

AC:

1156487

AN:

1458408

Hom.:

459740

Cov.:

AF XY:

0.793

AC XY:

575615

AN XY:

725798

show subpopulations

African (AFR)

AF:

0.883

AC:

29524

AN:

33418

American (AMR)

AF:

0.888

AC:

39698

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.816

AC:

21324

AN:

26118

East Asian (EAS)

AF:

0.815

AC:

32341

AN:

39692

South Asian (SAS)

AF:

0.828

AC:

71341

AN:

86186

European-Finnish (FIN)

AF:

0.744

AC:

39734

AN:

53380

Middle Eastern (MID)

AF:

0.824

AC:

4744

AN:

5760

European-Non Finnish (NFE)

AF:

0.784

AC:

869364

AN:

1108826

Other (OTH)

AF:

0.803

AC:

48417

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

13207

26414

39622

52829

66036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20598

41196

61794

82392

102990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.819

AC:

124677

AN:

152240

Hom.:

51244

Cov.:

AF XY:

0.816

AC XY:

60718

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.886

AC:

36785

AN:

41536

American (AMR)

AF:

0.842

AC:

12882

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.805

AC:

2792

AN:

3470

East Asian (EAS)

AF:

0.823

AC:

4263

AN:

5178

South Asian (SAS)

AF:

0.827

AC:

3991

AN:

4828

European-Finnish (FIN)

AF:

0.739

AC:

7836

AN:

10602

Middle Eastern (MID)

AF:

0.833

AC:

245

AN:

294

European-Non Finnish (NFE)

AF:

0.785

AC:

53406

AN:

68008

Other (OTH)

AF:

0.829

AC:

1750

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1168

2337

3505

4674

5842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

886

1772

2658

3544

4430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.803

Hom.:

149692

Bravo

AF:

0.832

Asia WGS

AF:

0.837

AC:

2906

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Immunodeficiency 51

Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

not provided

Benign:1Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Familial Candidiasis, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.3

(source)

DANN

Benign

0.61

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.020

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over