rs181990653

chr3-9933242-C-Gchr3-9933242-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_153460.4(IL17RC):c.1812C>G(p.Gly604=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00147 in 1,605,280 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. G604G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0018 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (22 hom.)
• Consequence: IL17RC NM_153460.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.178

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-9933242-C-G is Benign according to our data. Variant chr3-9933242-C-G is described in ClinVar as [Benign]. Clinvar id is 475924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.178 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00144 (2087/1452928) while in subpopulation AMR AF= 0.0216 (950/43916). AF 95% confidence interval is 0.0205. There are 22 homozygotes in gnomad4_exome. There are 1133 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RC	NM_153460.4	c.1812C>G	p.Gly604=	synonymous_variant	19/19	ENST00000403601.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RC	ENST00000403601.8	c.1812C>G	p.Gly604=	synonymous_variant	19/19	1	NM_153460.4	P4

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 267 AN: 152234 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00617

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00480 AC: 1092 AN: 227580 Hom.: 12 AF XY: 0.00445 AC XY: 554 AN XY: 124578

Gnomad AFR exome AF: 0.000279

Gnomad AMR exome AF: 0.0219

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00574

Gnomad SAS exome AF: 0.00805

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000605

Gnomad OTH exome AF: 0.00322

GnomAD4 exome AF: 0.00144 AC: 2087 AN: 1452928 Hom.: 22 Cov.: 34 AF XY: 0.00157 AC XY: 1133 AN XY: 722216

Gnomad4 AFR exome AF: 0.0000905

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00871

Gnomad4 SAS exome AF: 0.00807

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000244

Gnomad4 OTH exome AF: 0.00125

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152352 Hom.: 4 Cov.: 33 AF XY: 0.00207 AC XY: 154 AN XY: 74500

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000225 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.00520 AC: 18 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Candidiasis, familial, 9 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	-0.80
Cadd	Benign	6.1
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs181990653; hg19: chr3-9974926;