NM_017563.5:c.127-19574A>G

Variant names:

• chr3-57139887-T-C
• rs7374667
• NM_017563.5:c.127-19574A>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.127-19574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,074 control chromosomes in the GnomAD database, including 45,491 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 0.77 (45491 hom., cov: 32)
• Consequence: IL17RD NM_017563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RD	NM_017563.5	c.127-19574A>G		intron_variant	Intron 1 of 12	ENST00000296318.12	NP_060033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RD	ENST00000296318.12	c.127-19574A>G		intron_variant	Intron 1 of 12	1	NM_017563.5	ENSP00000296318.7

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116555 AN: 151956 Hom.: 45427 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.684

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.767 AC: 116672 AN: 152074 Hom.: 45491 Cov.: 32 AF XY: 0.766 AC XY: 56909 AN XY: 74306

African (AFR) AF: 0.905 AC: 37580 AN: 41516

American (AMR) AF: 0.811 AC: 12396 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1995 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3173 AN: 5180

South Asian (SAS) AF: 0.744 AC: 3586 AN: 4820

European-Finnish (FIN) AF: 0.684 AC: 7200 AN: 10520

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48311 AN: 67982

Other (OTH) AF: 0.753 AC: 1587 AN: 2108

Alfa AF: 0.731 Hom.: 47571

Bravo AF: 0.784

Asia WGS AF: 0.700 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.9
DANN	Benign	0.75
PhyloP100		-0.32
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: rs7374667; hg19: chr3-57173915;