NM_014339.7:c.932-10C>T

Variant names:

• chr22-17105581-C-T
• rs2241046
• NM_014339.7:c.932-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014339.7(IL17RA):​c.932-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 1,610,648 control chromosomes in the GnomAD database, including 510,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (51244 hom., cov: 33)
  • Exomes 𝑓: 0.79 (459740 hom.)
• Consequence: IL17RA NM_014339.7 intron
• Scores: Splicing: ADA: 0.00001350
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: -0.116
• Publications: 26 publications found

Genes affected

IL17RA (HGNC:5985): (interleukin 17 receptor A) Interleukin 17A (IL17A) is a proinflammatory cytokine secreted by activated T-lymphocytes. It is a potent inducer of the maturation of CD34-positive hematopoietic precursors into neutrophils. The transmembrane protein encoded by this gene (interleukin 17A receptor; IL17RA) is a ubiquitous type I membrane glycoprotein that binds with low affinity to interleukin 17A. Interleukin 17A and its receptor play a pathogenic role in many inflammatory and autoimmune diseases such as rheumatoid arthritis. Like other cytokine receptors, this receptor likely has a multimeric structure. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2014]

IL17RA Gene-Disease associations (from GenCC):

• immunodeficiency 51

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• chronic mucocutaneous candidiasis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-17105581-C-T is Benign according to our data. Variant chr22-17105581-C-T is described in ClinVar as Benign. ClinVar VariationId is 340585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014339.7. 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
	IL17RA	NM_014339.7	MANE Select	c.932-10C>T		intron	N/A	NP_055154.3
	IL17RA	NM_001289905.2		c.932-10C>T		intron	N/A	NP_001276834.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RA	ENST00000319363.11	TSL:1 MANE Select	c.932-10C>T		intron	N/A	ENSP00000320936.6
	IL17RA	ENST00000940705.1		c.932-272C>T		intron	N/A	ENSP00000610764.1
	IL17RA	ENST00000612619.2	TSL:5	c.932-10C>T		intron	N/A	ENSP00000479970.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124554 AN: 152122 Hom.: 51177 Cov.: 33

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.828

GnomAD2 exomes AF: 0.812 AC: 204298 AN: 251466 AF XY: 0.808

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.894

Gnomad ASJ exome AF: 0.819

Gnomad EAS exome AF: 0.820

Gnomad FIN exome AF: 0.744

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.793 AC: 1156487 AN: 1458408 Hom.: 459740 Cov.: 42 AF XY: 0.793 AC XY: 575615 AN XY: 725798

African (AFR) AF: 0.883 AC: 29524 AN: 33418

American (AMR) AF: 0.888 AC: 39698 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 21324 AN: 26118

East Asian (EAS) AF: 0.815 AC: 32341 AN: 39692

South Asian (SAS) AF: 0.828 AC: 71341 AN: 86186

European-Finnish (FIN) AF: 0.744 AC: 39734 AN: 53380

Middle Eastern (MID) AF: 0.824 AC: 4744 AN: 5760

European-Non Finnish (NFE) AF: 0.784 AC: 869364 AN: 1108826

Other (OTH) AF: 0.803 AC: 48417 AN: 60308

GnomAD4 genome AF: 0.819 AC: 124677 AN: 152240 Hom.: 51244 Cov.: 33 AF XY: 0.816 AC XY: 60718 AN XY: 74428

African (AFR) AF: 0.886 AC: 36785 AN: 41536

American (AMR) AF: 0.842 AC: 12882 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2792 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4263 AN: 5178

South Asian (SAS) AF: 0.827 AC: 3991 AN: 4828

European-Finnish (FIN) AF: 0.739 AC: 7836 AN: 10602

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53406 AN: 68008

Other (OTH) AF: 0.829 AC: 1750 AN: 2112

Alfa AF: 0.803 Hom.: 149692

Bravo AF: 0.832

Asia WGS AF: 0.837 AC: 2906 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Immunodeficiency 51 (4)
-	-	2	not specified (2)
-	-	1	Familial Candidiasis, Recessive (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.61
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs2241046; hg19: chr22-17586471;