rs6809523

Variant names:

• chr3-57099110-G-A
• rs6809523
• NM_017563.5:c.1165-572C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017563.5(IL17RD):​c.1165-572C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,100 control chromosomes in the GnomAD database, including 31,272 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31272 hom., cov: 32)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.692 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.1165-572C>T		intron	N/A	NP_060033.3
	IL17RD	NM_001318864.2		c.733-572C>T		intron	N/A	NP_001305793.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	ENST00000296318.12	TSL:1 MANE Select	c.1165-572C>T		intron	N/A	ENSP00000296318.7
	IL17RD	ENST00000320057.9	TSL:1	c.733-572C>T		intron	N/A	ENSP00000322250.5
	IL17RD	ENST00000463523.5	TSL:1	c.733-572C>T		intron	N/A	ENSP00000417516.1

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95731 AN: 151982 Hom.: 31266 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: 0.733

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.617

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.630 AC: 95775 AN: 152100 Hom.: 31272 Cov.: 32 AF XY: 0.627 AC XY: 46665 AN XY: 74386

African (AFR) AF: 0.577 AC: 23950 AN: 41474

American (AMR) AF: 0.546 AC: 8334 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3470

East Asian (EAS) AF: 0.129 AC: 665 AN: 5170

South Asian (SAS) AF: 0.677 AC: 3260 AN: 4818

European-Finnish (FIN) AF: 0.733 AC: 7763 AN: 10596

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

European-Non Finnish (NFE) AF: 0.698 AC: 47426 AN: 67978

Other (OTH) AF: 0.616 AC: 1304 AN: 2116

Alfa AF: 0.666 Hom.: 90575

Bravo AF: 0.610

Asia WGS AF: 0.417 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.43
PhyloP100		0.14
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: rs6809523; hg19: chr3-57133138;