rs41339945

Variant names:

• chr22-17104734-C-G
• rs41339945
• NM_014339.7:c.855C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-17104734-C-G
• chr22-17104734-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_014339.7(IL17RA):​c.855C>G​(p.Pro285Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000431 in 1,614,078 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: IL17RA NM_014339.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.250
• Publications: 0 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 22-17104734-C-G is Benign according to our data. Variant chr22-17104734-C-G is described in ClinVar as Benign. ClinVar VariationId is 542924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.25 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00223 (340/152280) while in subpopulation AFR AF = 0.00782 (325/41540). AF 95% confidence interval is 0.00712. There are 0 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

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.855C>G	p.Pro285Pro	synonymous	Exon 9 of 13	NP_055154.3
	IL17RA	NM_001289905.2		c.855C>G	p.Pro285Pro	synonymous	Exon 9 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.855C>G	p.Pro285Pro	synonymous	Exon 9 of 13	ENSP00000320936.6	Q96F46-1
	IL17RA	ENST00000940705.1		c.855C>G	p.Pro285Pro	synonymous	Exon 9 of 12	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.855C>G	p.Pro285Pro	synonymous	Exon 9 of 12	ENSP00000479970.1	Q96F46-2

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 340 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00785

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000529 AC: 133 AN: 251384 AF XY: 0.000353

Gnomad AFR exome AF: 0.00751

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000244 AC: 356 AN: 1461798 Hom.: 3 Cov.: 31 AF XY: 0.000204 AC XY: 148 AN XY: 727208

African (AFR) AF: 0.00905 AC: 303 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111936

Other (OTH) AF: 0.000497 AC: 30 AN: 60386

GnomAD4 genome AF: 0.00223 AC: 340 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.00210 AC XY: 156 AN XY: 74456

African (AFR) AF: 0.00782 AC: 325 AN: 41540

American (AMR) AF: 0.000588 AC: 9 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.000697 Hom.: 0

Bravo AF: 0.00240

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 51 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.6
DANN	Benign	0.71
PhyloP100		-0.25

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: rs41339945; hg19: chr22-17585624;