rs6780995

Variant names:

• chr3-57104391-G-A
• rs6780995
• NM_017563.5:c.764C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017563.5(IL17RD):​c.764C>T​(p.Thr255Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 1,602,056 control chromosomes in the GnomAD database, including 372,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (31279 hom., cov: 32)
  • Exomes 𝑓: 0.68 (341269 hom.)
• Consequence: IL17RD NM_017563.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.888
• Publications: 53 publications found

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]

IL17RD Gene-Disease associations (from GenCC):

• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypogonadotropic hypogonadism 18 with or without anosmia

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.384437E-6).
• BP6: Variant 3-57104391-G-A is Benign according to our data. Variant chr3-57104391-G-A is described in ClinVar as Benign. ClinVar VariationId is 1183074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017563.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	NM_017563.5	MANE Select	c.764C>T	p.Thr255Met	missense	Exon 8 of 13	NP_060033.3
	IL17RD	NM_001318864.2		c.332C>T	p.Thr111Met	missense	Exon 9 of 14	NP_001305793.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	ENST00000296318.12	TSL:1 MANE Select	c.764C>T	p.Thr255Met	missense	Exon 8 of 13	ENSP00000296318.7
	IL17RD	ENST00000320057.9	TSL:1	c.332C>T	p.Thr111Met	missense	Exon 9 of 14	ENSP00000322250.5
	IL17RD	ENST00000463523.5	TSL:1	c.332C>T	p.Thr111Met	missense	Exon 8 of 13	ENSP00000417516.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95726 AN: 151924 Hom.: 31272 Cov.: 32

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.619

GnomAD2 exomes AF: 0.619 AC: 152198 AN: 246056 AF XY: 0.631

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.122

Gnomad FIN exome AF: 0.738

Gnomad NFE exome AF: 0.695

Gnomad OTH exome AF: 0.652

GnomAD4 exome AF: 0.677 AC: 981949 AN: 1450014 Hom.: 341269 Cov.: 32 AF XY: 0.679 AC XY: 489529 AN XY: 721244

African (AFR) AF: 0.574 AC: 19096 AN: 33272

American (AMR) AF: 0.489 AC: 21604 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.651 AC: 16935 AN: 26012

East Asian (EAS) AF: 0.140 AC: 5547 AN: 39654

South Asian (SAS) AF: 0.715 AC: 60861 AN: 85154

European-Finnish (FIN) AF: 0.736 AC: 39216 AN: 53254

Middle Eastern (MID) AF: 0.690 AC: 3966 AN: 5750

European-Non Finnish (NFE) AF: 0.703 AC: 775257 AN: 1102758

Other (OTH) AF: 0.658 AC: 39467 AN: 59984

GnomAD4 genome AF: 0.630 AC: 95771 AN: 152042 Hom.: 31279 Cov.: 32 AF XY: 0.628 AC XY: 46633 AN XY: 74306

African (AFR) AF: 0.578 AC: 23962 AN: 41476

American (AMR) AF: 0.546 AC: 8336 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3468

East Asian (EAS) AF: 0.129 AC: 663 AN: 5156

South Asian (SAS) AF: 0.677 AC: 3253 AN: 4808

European-Finnish (FIN) AF: 0.732 AC: 7738 AN: 10564

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.698 AC: 47445 AN: 67980

Other (OTH) AF: 0.617 AC: 1304 AN: 2112

Alfa AF: 0.659 Hom.: 140106

Bravo AF: 0.610

TwinsUK AF: 0.708 AC: 2626

ALSPAC AF: 0.709 AC: 2733

ESP6500AA AF: 0.585 AC: 2576

ESP6500EA AF: 0.708 AC: 6087

ExAC AF: 0.624 AC: 75766

Asia WGS AF: 0.416 AC: 1453 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Hypogonadotropic hypogonadism 18 with or without anosmia Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.82	T
MetaRNN	Benign	0.0000024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.89
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.045
Sift	Benign	0.094	T
Sift4G	Benign	0.30	T
Polyphen		0.66	P
Vest4		0.19
MPC		0.24
ClinPred		0.017	T
GERP RS		-0.52
Varity_R		0.018
gMVP		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6780995; hg19: chr3-57138419; COSMIC: COSV56335199; COSMIC: COSV56335199;