rs75692599

Positions:

• chr3-9923898-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153460.4(IL17RC):​c.640G>A​(p.Val214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 1,614,080 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., cov: 31)
  • Exomes 𝑓: 0.016 (220 hom.)
• Consequence: IL17RC NM_153460.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0050364435).
• BP6: Variant 3-9923898-G-A is Benign according to our data. Variant chr3-9923898-G-A is described in ClinVar as [Benign]. Clinvar id is 475930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1841/152294) while in subpopulation NFE AF= 0.0184 (1252/68014). AF 95% confidence interval is 0.0176. There are 18 homozygotes in gnomad4. There are 869 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4	c.640G>A	p.Val214Met	missense_variant	8/19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8	c.640G>A	p.Val214Met	missense_variant	8/19	1	NM_153460.4	ENSP00000384969	P4

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1838 AN: 152176 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.0279

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0142 AC: 3565 AN: 251464 Hom.: 41 AF XY: 0.0142 AC XY: 1933 AN XY: 135902

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00963

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.00696

Gnomad FIN exome AF: 0.0155

Gnomad NFE exome AF: 0.0198

Gnomad OTH exome AF: 0.0197

GnomAD4 exome AF: 0.0161 AC: 23547 AN: 1461786 Hom.: 220 Cov.: 32 AF XY: 0.0160 AC XY: 11615 AN XY: 727194

Gnomad4 AFR exome AF: 0.00254

Gnomad4 AMR exome AF: 0.00977

Gnomad4 ASJ exome AF: 0.0248

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00667

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0121 AC: 1841 AN: 152294 Hom.: 18 Cov.: 31 AF XY: 0.0117 AC XY: 869 AN XY: 74480

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.0279

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0184

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0172 Hom.: 39

Bravo AF: 0.0118

ESP6500AA AF: 0.00227 AC: 10

ESP6500EA AF: 0.0235 AC: 202

ExAC AF: 0.0150 AC: 1824

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.0209

EpiControl AF: 0.0218

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Candidiasis, familial, 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;.;.;T;.;.;.;.;.
Eigen	Benign	0.0048
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D;D;D
MetaRNN	Benign	0.0050	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;.;.;L;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	.;N;N;N;.;N;N;N;N
REVEL	Benign	0.072
Sift	Uncertain	0.0020	.;D;D;D;.;D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D;.;D;D;D;D
Polyphen		0.97, 1.0	.;D;.;D;D;.;D;.;.
Vest4		0.36
MPC		0.60
ClinPred		0.022	T
GERP RS		2.2
Varity_R		0.16
gMVP		0.35

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: rs75692599; hg19: chr3-9965582; COSMIC: COSV55972341; COSMIC: COSV55972341;