3-57096633-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1396 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17RD	NM_017563.5	c.2108-128G>A		intron_variant		ENST00000296318.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17RD	ENST00000296318.12	c.2108-128G>A		intron_variant		1	NM_017563.5	P1
IL17RD	ENST00000320057.9	c.1676-128G>A		intron_variant		1
IL17RD	ENST00000463523.5	c.1676-128G>A		intron_variant		1

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

Gnomad4 AFR exome AF: 0.0312

Gnomad4 AMR exome AF: 0.00315

Gnomad4 ASJ exome AF: 0.000613

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000550

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000145

Gnomad4 OTH exome AF: 0.00245

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

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00666 Hom.: 0

Bravo AF: 0.0102

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.2
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs115706543; hg19: chr3-57130661;