3-57119841-C-T

Variant names:

• chr3-57119841-C-T
• rs747089
• NM_017563.5:c.184+415G>A

Variant summary

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

The NM_017563.5(IL17RD):​c.184+415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,200 control chromosomes in the GnomAD database, including 2,475 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 0.16 (2475 hom., cov: 32)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 7 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=-0.88).
• 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 rank	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.184+415G>A		intron_variant	Intron 2 of 12	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.184+415G>A		intron_variant	Intron 2 of 12	1	NM_017563.5	ENSP00000296318.7

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24123 AN: 152082 Hom.: 2468 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.159 AC: 24145 AN: 152200 Hom.: 2475 Cov.: 32 AF XY: 0.164 AC XY: 12235 AN XY: 74402

African (AFR) AF: 0.0679 AC: 2820 AN: 41534

American (AMR) AF: 0.287 AC: 4396 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.366 AC: 1897 AN: 5176

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1745 AN: 10584

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10915 AN: 68002

Other (OTH) AF: 0.175 AC: 371 AN: 2114

Alfa AF: 0.168 Hom.: 1341

Bravo AF: 0.163

Asia WGS AF: 0.304 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.44
PhyloP100		0.19
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: rs747089; hg19: chr3-57153869;