chr3-57126284-T-C

Variant names:

• chr3-57126284-T-C
• rs12495640
• NM_017563.5:c.127-5971A>G

Variant summary

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

The NM_017563.5(IL17RD):​c.127-5971A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,094 control chromosomes in the GnomAD database, including 15,478 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 0.45 (15478 hom., cov: 32)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 5 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=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 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.127-5971A>G		intron	N/A	NP_060033.3
	IL17RD	NM_001318864.2		c.-306-5971A>G		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.127-5971A>G		intron	N/A	ENSP00000296318.7
	IL17RD	ENST00000320057.9	TSL:1	c.-306-5971A>G		intron	N/A	ENSP00000322250.5
	IL17RD	ENST00000463523.5	TSL:1	c.-306-5971A>G		intron	N/A	ENSP00000417516.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67734 AN: 151976 Hom.: 15435 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.446 AC: 67826 AN: 152094 Hom.: 15478 Cov.: 32 AF XY: 0.447 AC XY: 33266 AN XY: 74338

African (AFR) AF: 0.519 AC: 21547 AN: 41484

American (AMR) AF: 0.520 AC: 7955 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1022 AN: 3472

East Asian (EAS) AF: 0.409 AC: 2110 AN: 5162

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4814

European-Finnish (FIN) AF: 0.424 AC: 4483 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27551 AN: 67986

Other (OTH) AF: 0.432 AC: 911 AN: 2108

Alfa AF: 0.419 Hom.: 22551

Bravo AF: 0.457

Asia WGS AF: 0.419 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.57
PhyloP100		2.6
Mutation Taster		=92/8	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: rs12495640; hg19: chr3-57160312;