NM_017563.5:c.2108-128G>A

Variant names:

• chr3-57096633-C-T
• rs115706543
• NM_017563.5:c.2108-128G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017563.5(IL17RD):​c.2108-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 688,420 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (9 hom.)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 3-57096633-C-T is Benign according to our data. Variant chr3-57096633-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1216835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00919 (1399/152240) while in subpopulation AFR AF = 0.0319 (1325/41546). AF 95% confidence interval is 0.0305. There are 27 homozygotes in GnomAd4. There are 668 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1399 AD gene.

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.2108-128G>A		intron	N/A	NP_060033.3	Q8NFM7-1
	IL17RD	NM_001318864.2		c.1676-128G>A		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.2108-128G>A		intron	N/A	ENSP00000296318.7	Q8NFM7-1
	IL17RD	ENST00000320057.9	TSL:1	c.1676-128G>A		intron	N/A	ENSP00000322250.5	Q8NFM7-2
	IL17RD	ENST00000463523.5	TSL:1	c.1676-128G>A		intron	N/A	ENSP00000417516.1	Q8NFM7-2

Frequencies

GnomAD3 genomes AF: 0.00918 AC: 1396 AN: 152122 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00282

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00131 AC: 701 AN: 536180 Hom.: 9 AF XY: 0.00105 AC XY: 299 AN XY: 285510

African (AFR) AF: 0.0312 AC: 473 AN: 15166

American (AMR) AF: 0.00315 AC: 94 AN: 29816

Ashkenazi Jewish (ASJ) AF: 0.000613 AC: 10 AN: 16314

East Asian (EAS) AF: 0.00 AC: 0 AN: 33614

South Asian (SAS) AF: 0.0000550 AC: 3 AN: 54520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43610

Middle Eastern (MID) AF: 0.00133 AC: 4 AN: 3010

European-Non Finnish (NFE) AF: 0.000145 AC: 45 AN: 310786

Other (OTH) AF: 0.00245 AC: 72 AN: 29344

GnomAD4 genome AF: 0.00919 AC: 1399 AN: 152240 Hom.: 27 Cov.: 32 AF XY: 0.00898 AC XY: 668 AN XY: 74420

African (AFR) AF: 0.0319 AC: 1325 AN: 41546

American (AMR) AF: 0.00281 AC: 43 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68016

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.00796 Hom.: 0

Bravo AF: 0.0102

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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: rs115706543; hg19: chr3-57130661;