3-57097731-T-C

Variant summary

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

The NM_017563.5(IL17RD):c.1972A>G(p.Met658Val) variant causes a missense change. The variant allele was found at a frequency of 0.000315 in 1,602,970 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.82

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=0.0065295994).
• BP6: Variant 3-57097731-T-C is Benign according to our data. Variant chr3-57097731-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 677804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000427 (65/152296) while in subpopulation EAS AF= 0.0116 (60/5172). AF 95% confidence interval is 0.00925. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 65 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RD	NM_017563.5	c.1972A>G	p.Met658Val	missense_variant	12/13	ENST00000296318.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RD	ENST00000296318.12	c.1972A>G	p.Met658Val	missense_variant	12/13	1	NM_017563.5	P1
IL17RD	ENST00000320057.9	c.1540A>G	p.Met514Val	missense_variant	13/14	1
IL17RD	ENST00000463523.5	c.1540A>G	p.Met514Val	missense_variant	12/13	1
IL17RD	ENST00000469841.5	n.1909A>G		non_coding_transcript_exon_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.000427 AC: 65 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0116

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00106 AC: 254 AN: 239236 Hom.: 1 AF XY: 0.00110 AC XY: 142 AN XY: 129454

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0135

Gnomad SAS exome AF: 0.000281

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000303 AC: 440 AN: 1450674 Hom.: 1 Cov.: 32 AF XY: 0.000276 AC XY: 199 AN XY: 720214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000228

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00990

Gnomad4 SAS exome AF: 0.000213

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.000452

GnomAD4 genome AF: 0.000427 AC: 65 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42 AN XY: 74468

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0116

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000295 Hom.: 0

Bravo AF: 0.000703

ExAC AF: 0.00105 AC: 127

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Invitae	May 18, 2022	- -

IL17RD-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	17
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;.;D
MetaRNN	Benign	0.0065	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.81	N;N;N;.
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Polyphen		0.15	B;.;.;.
Vest4		0.42
MVP		0.40
MPC		0.13
ClinPred		0.026	T
GERP RS		5.8
Varity_R		0.39
gMVP		0.31

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: rs140930246; hg19: chr3-57131759;