rs115461448

Positions:

• chr3-9928397-G-A

Variant summary

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

The ENST00000403601.8(IL17RC):​c.970G>A​(p.Ala324Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0141 in 1,604,258 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (21 hom., cov: 33)
  • Exomes 𝑓: 0.014 (184 hom.)
• Consequence: IL17RC ENST00000403601.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.71

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=0.0069948733).
• BP6: Variant 3-9928397-G-A is Benign according to our data. Variant chr3-9928397-G-A is described in ClinVar as [Benign]. Clinvar id is 475918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0118 (1805/152378) while in subpopulation SAS AF= 0.0184 (89/4832). AF 95% confidence interval is 0.0153. There are 21 homozygotes in gnomad4. There are 931 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RC	NM_153460.4	c.970G>A	p.Ala324Thr	missense_variant	11/19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RC	ENST00000403601.8	c.970G>A	p.Ala324Thr	missense_variant	11/19	1	NM_153460.4	ENSP00000384969	P4

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1799 AN: 152260 Hom.: 19 Cov.: 33

Gnomad AFR AF: 0.00463

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0121 AC: 2921 AN: 241526 Hom.: 28 AF XY: 0.0125 AC XY: 1643 AN XY: 131710

Gnomad AFR exome AF: 0.00506

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00465

Gnomad EAS exome AF: 0.00134

Gnomad SAS exome AF: 0.0164

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.0146

Gnomad OTH exome AF: 0.0119

GnomAD4 exome AF: 0.0144 AC: 20891 AN: 1451880 Hom.: 184 Cov.: 41 AF XY: 0.0144 AC XY: 10428 AN XY: 721828

Gnomad4 AFR exome AF: 0.00398

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00514

Gnomad4 EAS exome AF: 0.00159

Gnomad4 SAS exome AF: 0.0168

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0130

GnomAD4 genome AF: 0.0118 AC: 1805 AN: 152378 Hom.: 21 Cov.: 33 AF XY: 0.0125 AC XY: 931 AN XY: 74516

Gnomad4 AFR AF: 0.00459

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0147 Hom.: 31

Bravo AF: 0.0117

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0184 AC: 71

ESP6500AA AF: 0.00568 AC: 25

ESP6500EA AF: 0.0172 AC: 148

ExAC AF: 0.0115 AC: 1392

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.0156

EpiControl AF: 0.0148

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

Jan 31, 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	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	.;.;.;T;.;.;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.78	T;.;T;T;T;T;T;T;T
MetaRNN	Benign	0.0070	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;.;.;L;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.9	.;N;N;N;.;N;N;N;N
REVEL	Benign	0.091
Sift	Benign	0.10	.;T;T;T;.;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;.;T;T;T;T
Polyphen		0.70, 1.0, 0.51	.;P;.;D;P;.;P;.;.
Vest4		0.25
MPC		0.44
ClinPred		0.015	T
GERP RS		4.1
Varity_R		0.19
gMVP		0.62

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: rs115461448; hg19: chr3-9970081;