3-9928347-A-G

Variant names:

• chr3-9928347-A-G
• rs279549
• NM_153460.4:c.920A>G

Variant summary

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

The NM_153460.4(IL17RC):​c.920A>G​(p.Gln307Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,603,840 control chromosomes in the GnomAD database, including 792,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (75524 hom., cov: 34)
  • Exomes 𝑓: 0.99 (717326 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.08
• Publications: 28 publications found

Genes affected

IL17RC (HGNC:18358): (interleukin 17 receptor C) This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling. [provided by RefSeq, Feb 2011]

IL17RC Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• candidiasis, familial, 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.66898E-7).
• BP6: Variant 3-9928347-A-G is Benign according to our data. Variant chr3-9928347-A-G is described in ClinVar as Benign. ClinVar VariationId is 1164863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153460.4. 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
	IL17RC	NM_153460.4	MANE Select	c.920A>G	p.Gln307Arg	missense	Exon 11 of 19	NP_703190.2	Q8NAC3-2
	IL17RC	NM_153461.4		c.1133A>G	p.Gln378Arg	missense	Exon 11 of 19	NP_703191.2	Q8NAC3-1
	IL17RC	NM_001203263.2		c.920A>G	p.Gln307Arg	missense	Exon 11 of 18	NP_001190192.2	Q8NAC3-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RC	ENST00000403601.8	TSL:1 MANE Select	c.920A>G	p.Gln307Arg	missense	Exon 11 of 19	ENSP00000384969.3	Q8NAC3-2
	IL17RC	ENST00000413608.2	TSL:1	c.920A>G	p.Gln307Arg	missense	Exon 11 of 18	ENSP00000396064.1	Q8NAC3-5
	IL17RC	ENST00000383812.9	TSL:1	c.875A>G	p.Gln292Arg	missense	Exon 10 of 18	ENSP00000373323.4	Q8NAC3-3

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151585 AN: 152242 Hom.: 75465 Cov.: 34

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.994

GnomAD2 exomes AF: 0.995 AC: 245455 AN: 246602 AF XY: 0.995

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.993

Gnomad OTH exome AF: 0.996

GnomAD4 exome AF: 0.994 AC: 1443034 AN: 1451480 Hom.: 717326 Cov.: 66 AF XY: 0.994 AC XY: 716275 AN XY: 720402

African (AFR) AF: 0.999 AC: 33169 AN: 33210

American (AMR) AF: 0.995 AC: 43847 AN: 44064

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25584 AN: 25748

East Asian (EAS) AF: 1.00 AC: 39464 AN: 39464

South Asian (SAS) AF: 0.998 AC: 85508 AN: 85668

European-Finnish (FIN) AF: 0.999 AC: 52677 AN: 52726

Middle Eastern (MID) AF: 0.994 AC: 5688 AN: 5720

European-Non Finnish (NFE) AF: 0.993 AC: 1097511 AN: 1104982

Other (OTH) AF: 0.995 AC: 59586 AN: 59898

GnomAD4 genome AF: 0.996 AC: 151703 AN: 152360 Hom.: 75524 Cov.: 34 AF XY: 0.996 AC XY: 74196 AN XY: 74494

African (AFR) AF: 0.998 AC: 41516 AN: 41580

American (AMR) AF: 0.995 AC: 15243 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3448 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5166 AN: 5166

South Asian (SAS) AF: 0.999 AC: 4829 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10632

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67564 AN: 68042

Other (OTH) AF: 0.994 AC: 2104 AN: 2116

Alfa AF: 0.994 Hom.: 95461

Bravo AF: 0.995

TwinsUK AF: 0.996 AC: 3692

ALSPAC AF: 0.994 AC: 3829

ESP6500AA AF: 0.999 AC: 4401

ESP6500EA AF: 0.994 AC: 8543

ExAC AF: 0.996 AC: 120744

Asia WGS AF: 1.00 AC: 3478 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Candidiasis, familial, 9 (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.88
DANN	Benign	0.097
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	6.7e-7	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.95	N
PhyloP100		-1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.25
ClinPred		0.0021	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.31
Mutation Taster		=99/1	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: rs279549; hg19: chr3-9970031; COSMIC: COSV107353403; COSMIC: COSV107353403;