rs17057718

Positions:

• chr3-57102557-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017563.5(IL17RD):​c.901G>A​(p.Val301Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,574,568 control chromosomes in the GnomAD database, including 25,963 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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (2470 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23493 hom.)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49

Genes affected

IL17RD (HGNC:17616): (interleukin 17 receptor D) This gene encodes a membrane protein belonging to the interleukin-17 receptor (IL-17R) protein family. The encoded protein is a component of the interleukin-17 receptor signaling complex, and the interaction between this protein and IL-17R does not require the interleukin. The gene product also affects fibroblast growth factor signaling, inhibiting or stimulating growth through MAPK/ERK signaling. Alternate splicing generates multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021972358).
• BP6: Variant 3-57102557-C-T is Benign according to our data. Variant chr3-57102557-C-T is described in ClinVar as [Benign]. Clinvar id is 1262347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RD	NM_017563.5	c.901G>A	p.Val301Met	missense_variant	10/13	ENST00000296318.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RD	ENST00000296318.12	c.901G>A	p.Val301Met	missense_variant	10/13	1	NM_017563.5	P1
IL17RD	ENST00000320057.9	c.469G>A	p.Val157Met	missense_variant	11/14	1
IL17RD	ENST00000463523.5	c.469G>A	p.Val157Met	missense_variant	10/13	1
IL17RD	ENST00000469841.5	n.838G>A		non_coding_transcript_exon_variant	10/12	2

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24098 AN: 151008 Hom.: 2463 Cov.: 33

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.178

GnomAD3 exomes AF: 0.204 AC: 50695 AN: 248048 Hom.: 6375 AF XY: 0.200 AC XY: 26834 AN XY: 134170

Gnomad AFR exome AF: 0.0638

Gnomad AMR exome AF: 0.367

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.205

Gnomad FIN exome AF: 0.160

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.172 AC: 244330 AN: 1423434 Hom.: 23493 Cov.: 29 AF XY: 0.173 AC XY: 121487 AN XY: 704168

Gnomad4 AFR exome AF: 0.0609

Gnomad4 AMR exome AF: 0.356

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.365

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.175

GnomAD4 genome AF: 0.160 AC: 24124 AN: 151134 Hom.: 2470 Cov.: 33 AF XY: 0.165 AC XY: 12228 AN XY: 73900

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.178

Alfa AF: 0.169 Hom.: 5096

Bravo AF: 0.163

TwinsUK AF: 0.147 AC: 545

ALSPAC AF: 0.155 AC: 597

ESP6500AA AF: 0.0719 AC: 317

ESP6500EA AF: 0.152 AC: 1306

ExAC AF: 0.196 AC: 23760

Asia WGS AF: 0.305 AC: 1056 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.88
DEOGEN2	Benign	0.051	T;.;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.82	T;.;.;T
MetaRNN	Benign	0.0022	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.34	N;.;.;.
MutationTaster	Benign	0.040	P;P;P;P
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.30	N;N;N;.
REVEL	Benign	0.085
Sift	Benign	0.35	T;T;T;.
Sift4G	Benign	0.39	T;T;T;.
Polyphen		0.47	P;.;.;.
Vest4		0.16
MPC		0.30
ClinPred		0.014	T
GERP RS		3.6
Varity_R		0.030
gMVP		0.27

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: rs17057718; hg19: chr3-57136585; COSMIC: COSV56338664; COSMIC: COSV56338664;