3-57096633-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017563.5(IL17RD):​c.2108-128G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 536,182 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000187 AC: 1 AN: 536182 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 285512

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15168

American (AMR) AF: 0.00 AC: 0 AN: 29816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16314

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54520

European-Finnish (FIN) AF: 0.0000229 AC: 1 AN: 43610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3010

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 310786

Other (OTH) AF: 0.00 AC: 0 AN: 29344

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.7
DANN	Benign	0.77
PhyloP100		-0.12

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;