rs6810042

Variant names:

• chr3-57123688-G-A
• rs6810042
• NM_017563.5:c.127-3375C>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.127-3375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,138 control chromosomes in the GnomAD database, including 3,719 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 0.20 (3719 hom., cov: 32)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	NM_017563.5	MANE Select	c.127-3375C>T		intron	N/A	NP_060033.3	Q8NFM7-1
	IL17RD	NM_001318864.2		c.-306-3375C>T		intron	N/A	NP_001305793.1	Q8NFM7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RD	ENST00000296318.12	TSL:1 MANE Select	c.127-3375C>T		intron	N/A	ENSP00000296318.7	Q8NFM7-1
	IL17RD	ENST00000320057.9	TSL:1	c.-306-3375C>T		intron	N/A	ENSP00000322250.5	Q8NFM7-2
	IL17RD	ENST00000463523.5	TSL:1	c.-306-3375C>T		intron	N/A	ENSP00000417516.1	Q8NFM7-2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31183 AN: 152020 Hom.: 3715 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.205 AC: 31188 AN: 152138 Hom.: 3719 Cov.: 32 AF XY: 0.201 AC XY: 14933 AN XY: 74384

African (AFR) AF: 0.103 AC: 4289 AN: 41518

American (AMR) AF: 0.208 AC: 3174 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3468

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5180

South Asian (SAS) AF: 0.121 AC: 583 AN: 4824

European-Finnish (FIN) AF: 0.253 AC: 2676 AN: 10568

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19073 AN: 67986

Other (OTH) AF: 0.202 AC: 425 AN: 2108

Alfa AF: 0.256 Hom.: 8743

Bravo AF: 0.200

Asia WGS AF: 0.0830 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		-0.75
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: rs6810042; hg19: chr3-57157716;