rs17205308

Variant names:

• chr22-17101987-G-T
• rs17205308
• NM_014339.7:c.551-9G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(IL17RA):​c.551-9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,614,086 control chromosomes in the GnomAD database, including 301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (43 hom., cov: 32)
  • Exomes 𝑓: 0.0056 (258 hom.)
• Consequence: IL17RA NM_014339.7 intron
• Scores: Splicing: ADA: 0.00003007
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.203
• Publications: 5 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 (BayesDel_noAF=-0.88).
• BP6: Variant 22-17101987-G-T is Benign according to our data. Variant chr22-17101987-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 340574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

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.551-9G>T		intron	N/A	NP_055154.3
	IL17RA	NM_001289905.2		c.551-9G>T		intron	N/A	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.551-9G>T		intron	N/A	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.551-9G>T		intron	N/A	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.551-9G>T		intron	N/A	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00978 AC: 1487 AN: 152088 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00816

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.0151 AC: 3792 AN: 251458 AF XY: 0.0134

Gnomad AFR exome AF: 0.00695

Gnomad AMR exome AF: 0.0366

Gnomad ASJ exome AF: 0.000893

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00151

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.00558 AC: 8154 AN: 1461880 Hom.: 258 Cov.: 33 AF XY: 0.00546 AC XY: 3973 AN XY: 727242

African (AFR) AF: 0.00923 AC: 309 AN: 33480

American (AMR) AF: 0.0359 AC: 1604 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000574 AC: 15 AN: 26136

East Asian (EAS) AF: 0.0933 AC: 3703 AN: 39700

South Asian (SAS) AF: 0.0105 AC: 902 AN: 86256

European-Finnish (FIN) AF: 0.000374 AC: 20 AN: 53416

Middle Eastern (MID) AF: 0.0137 AC: 79 AN: 5766

European-Non Finnish (NFE) AF: 0.000927 AC: 1031 AN: 1112008

Other (OTH) AF: 0.00813 AC: 491 AN: 60396

GnomAD4 genome AF: 0.00978 AC: 1489 AN: 152206 Hom.: 43 Cov.: 32 AF XY: 0.0110 AC XY: 816 AN XY: 74416

African (AFR) AF: 0.00813 AC: 338 AN: 41556

American (AMR) AF: 0.0312 AC: 477 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 515 AN: 5162

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4828

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 67986

Other (OTH) AF: 0.0114 AC: 24 AN: 2108

Alfa AF: 0.00467 Hom.: 7

Bravo AF: 0.0120

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00207

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.1
DANN	Benign	0.53
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 31

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17205308; hg19: chr22-17582877; COSMIC: COSV60052259; COSMIC: COSV60052259;