chr22-17085084-G-C

Variant names:

• chr22-17085084-G-C
• rs917865
• NM_014339.7:c.-8G>C

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.-8G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 1,315,154 control chromosomes in the GnomAD database, including 430,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (53550 hom., cov: 34)
  • Exomes 𝑓: 0.80 (377345 hom.)
• Consequence: IL17RA NM_014339.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.04
• Publications: 10 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=-0.86).
• BP6: Variant 22-17085084-G-C is Benign according to our data. Variant chr22-17085084-G-C is described in ClinVar as Benign. ClinVar VariationId is 340561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.952 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.-8G>C		5_prime_UTR	Exon 1 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.-8G>C		5_prime_UTR	Exon 1 of 12	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.-8G>C		5_prime_UTR	Exon 1 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.-8G>C		5_prime_UTR	Exon 1 of 12	ENSP00000610764.1
	IL17RA	ENST00000962147.1		c.-8G>C		5_prime_UTR	Exon 1 of 10	ENSP00000632206.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126564 AN: 152026 Hom.: 53500 Cov.: 34

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.867

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.818

GnomAD2 exomes AF: 0.804 AC: 2525 AN: 3142 AF XY: 0.802

Gnomad AFR exome AF: 0.974

Gnomad AMR exome AF: 0.676

Gnomad ASJ exome AF: 0.865

Gnomad EAS exome AF: 0.713

Gnomad FIN exome AF: 0.859

Gnomad NFE exome AF: 0.818

Gnomad OTH exome AF: 0.810

GnomAD4 exome AF: 0.804 AC: 935247 AN: 1163018 Hom.: 377345 Cov.: 52 AF XY: 0.804 AC XY: 450580 AN XY: 560162

African (AFR) AF: 0.969 AC: 22692 AN: 23408

American (AMR) AF: 0.599 AC: 5361 AN: 8950

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 12867 AN: 15708

East Asian (EAS) AF: 0.607 AC: 16303 AN: 26864

South Asian (SAS) AF: 0.795 AC: 34827 AN: 43800

European-Finnish (FIN) AF: 0.833 AC: 22630 AN: 27176

Middle Eastern (MID) AF: 0.873 AC: 4103 AN: 4700

European-Non Finnish (NFE) AF: 0.807 AC: 778632 AN: 965142

Other (OTH) AF: 0.800 AC: 37832 AN: 47270

GnomAD4 genome AF: 0.833 AC: 126662 AN: 152136 Hom.: 53550 Cov.: 34 AF XY: 0.829 AC XY: 61676 AN XY: 74378

African (AFR) AF: 0.960 AC: 39890 AN: 41544

American (AMR) AF: 0.658 AC: 10063 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2811 AN: 3468

East Asian (EAS) AF: 0.606 AC: 3107 AN: 5124

South Asian (SAS) AF: 0.765 AC: 3690 AN: 4824

European-Finnish (FIN) AF: 0.842 AC: 8934 AN: 10606

Middle Eastern (MID) AF: 0.925 AC: 270 AN: 292

European-Non Finnish (NFE) AF: 0.815 AC: 55381 AN: 67958

Other (OTH) AF: 0.817 AC: 1725 AN: 2112

Alfa AF: 0.834 Hom.: 6620

Bravo AF: 0.821

Asia WGS AF: 0.681 AC: 2360 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	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	-0.86
CADD	Benign	9.0
DANN	Benign	0.73
PhyloP100		1.0
PromoterAI		0.045	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs917865; hg19: chr22-17565974;