NM_014339.7:c.1137G>A

Variant names:

• chr22-17108356-G-A
• rs879576
• NM_014339.7:c.1137G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014339.7(IL17RA):​c.1137G>A​(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,960 control chromosomes in the GnomAD database, including 12,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1892 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10907 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.31
• Publications: 24 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 22-17108356-G-A is Benign according to our data. Variant chr22-17108356-G-A is described in ClinVar as Benign. ClinVar VariationId is 340592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 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.1137G>A	p.Lys379Lys	synonymous	Exon 13 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.1035G>A	p.Lys345Lys	synonymous	Exon 12 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.1137G>A	p.Lys379Lys	synonymous	Exon 13 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.1125G>A	p.Lys375Lys	synonymous	Exon 12 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.1035G>A	p.Lys345Lys	synonymous	Exon 12 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22154 AN: 152056 Hom.: 1890 Cov.: 33

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.151

GnomAD2 exomes AF: 0.114 AC: 28544 AN: 251174 AF XY: 0.115

Gnomad AFR exome AF: 0.236

Gnomad AMR exome AF: 0.0759

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.117

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.116 AC: 169645 AN: 1461784 Hom.: 10907 Cov.: 54 AF XY: 0.117 AC XY: 84805 AN XY: 727198

African (AFR) AF: 0.232 AC: 7780 AN: 33480

American (AMR) AF: 0.0798 AC: 3570 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5970 AN: 26132

East Asian (EAS) AF: 0.000327 AC: 13 AN: 39700

South Asian (SAS) AF: 0.111 AC: 9558 AN: 86258

European-Finnish (FIN) AF: 0.113 AC: 6016 AN: 53378

Middle Eastern (MID) AF: 0.233 AC: 1344 AN: 5762

European-Non Finnish (NFE) AF: 0.115 AC: 127745 AN: 1111962

Other (OTH) AF: 0.127 AC: 7649 AN: 60392

GnomAD4 genome AF: 0.146 AC: 22171 AN: 152176 Hom.: 1892 Cov.: 33 AF XY: 0.144 AC XY: 10679 AN XY: 74394

African (AFR) AF: 0.229 AC: 9506 AN: 41492

American (AMR) AF: 0.120 AC: 1842 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 792 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5170

South Asian (SAS) AF: 0.106 AC: 512 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7887 AN: 67998

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.121 Hom.: 1852

Bravo AF: 0.150

Asia WGS AF: 0.0580 AC: 202 AN: 3478

EpiCase AF: 0.129

EpiControl AF: 0.126

ClinVar

ClinVar submissions

Significance: 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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	6.9
DANN	Benign	0.60
PhyloP100		1.3
Mutation Taster		=100/0	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: rs879576; hg19: chr22-17589246;