rs17205308

chr22-17101987-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(IL17RA):c.551-9G>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003007
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.203

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RA	NM_014339.7	c.551-9G>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000319363.11
IL17RA	NM_001289905.2	c.551-9G>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RA	ENST00000319363.11	c.551-9G>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014339.7	P2

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

GnomAD3 exomes AF: 0.0151 AC: 3792 AN: 251458 Hom.: 125 AF XY: 0.0134 AC XY: 1822 AN XY: 135920

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 SAS exome AF: 0.00993

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

Gnomad4 AFR exome AF: 0.00923

Gnomad4 AMR exome AF: 0.0359

Gnomad4 ASJ exome AF: 0.000574

Gnomad4 EAS exome AF: 0.0933

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.000374

Gnomad4 NFE exome AF: 0.000927

Gnomad4 OTH exome AF: 0.00813

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

Gnomad4 AFR AF: 0.00813

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00463 Hom.: 6

Bravo AF: 0.0120

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.00164

EpiControl AF: 0.00207

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial Candidiasis, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Immunodeficiency 51 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.1
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

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