chr3-9917263-T-TG

Variant names:

• chr3-9917263-T-TG
• rs530330109
• ENST00000451271.5:n.-44dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000683484.1(ENSG00000288550):​n.-44dupG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12370 hom., cov: 0)
  • Exomes 𝑓: 0.34 (36723 hom.)
• Consequence: ENSG00000288550 ENST00000683484.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0890
• Publications: 1 publications found

Genes affected

IL17RC (HGNC:18358): (interleukin 17 receptor C) This gene encodes a single-pass type I membrane protein that shares similarity with the interleukin-17 receptor (IL-17RA). Unlike IL-17RA, which is predominantly expressed in hemopoietic cells, and binds with high affinity to only IL-17A, this protein is expressed in nonhemopoietic tissues, and binds both IL-17A and IL-17F with similar affinities. The proinflammatory cytokines, IL-17A and IL-17F, have been implicated in the progression of inflammatory and autoimmune diseases. Multiple alternatively spliced transcript variants encoding different isoforms have been detected for this gene, and it has been proposed that soluble, secreted proteins lacking transmembrane and intracellular domains may function as extracellular antagonists to cytokine signaling. [provided by RefSeq, Feb 2011]

IL17RC Gene-Disease associations (from GenCC):

• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• candidiasis, familial, 9

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000288550 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-9917263-T-TG is Benign according to our data. Variant chr3-9917263-T-TG is described in ClinVar as [Benign]. Clinvar id is 2688239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RC	NM_153460.4	c.-44dupG		5_prime_UTR_variant	Exon 1 of 19	ENST00000403601.8	NP_703190.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288550	ENST00000683484.1	n.-44dupG		non_coding_transcript_exon_variant	Exon 1 of 24			ENSP00000507040.1
IL17RC	ENST00000403601.8	c.-44dupG		5_prime_UTR_variant	Exon 1 of 19	1	NM_153460.4	ENSP00000384969.3
ENSG00000288550	ENST00000683484.1	n.-44dupG		5_prime_UTR_variant	Exon 1 of 24			ENSP00000507040.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 58895 AN: 149906 Hom.: 12336 Cov.: 0

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.402

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.345 AC: 379929 AN: 1101444 Hom.: 36723 Cov.: 20 AF XY: 0.344 AC XY: 188247 AN XY: 547664

African (AFR) AF: 0.488 AC: 11975 AN: 24514

American (AMR) AF: 0.307 AC: 7524 AN: 24514

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 5354 AN: 17924

East Asian (EAS) AF: 0.110 AC: 3147 AN: 28544

South Asian (SAS) AF: 0.343 AC: 21479 AN: 62668

European-Finnish (FIN) AF: 0.380 AC: 16347 AN: 43056

Middle Eastern (MID) AF: 0.283 AC: 991 AN: 3506

European-Non Finnish (NFE) AF: 0.350 AC: 297541 AN: 851202

Other (OTH) AF: 0.342 AC: 15571 AN: 45516

GnomAD4 genome AF: 0.393 AC: 58985 AN: 150012 Hom.: 12370 Cov.: 0 AF XY: 0.393 AC XY: 28754 AN XY: 73226

African (AFR) AF: 0.543 AC: 22283 AN: 41056

American (AMR) AF: 0.311 AC: 4716 AN: 15150

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 967 AN: 3432

East Asian (EAS) AF: 0.0889 AC: 448 AN: 5038

South Asian (SAS) AF: 0.354 AC: 1666 AN: 4700

European-Finnish (FIN) AF: 0.402 AC: 4106 AN: 10222

Middle Eastern (MID) AF: 0.215 AC: 62 AN: 288

European-Non Finnish (NFE) AF: 0.353 AC: 23721 AN: 67136

Other (OTH) AF: 0.348 AC: 727 AN: 2092

Alfa AF: 0.213 Hom.: 413

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.089
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs530330109; hg19: chr3-9958947; COSMIC: COSV55968522; COSMIC: COSV55968522;