22-17102216-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1

The ENST00000319363.11(IL17RA):ā€‹c.676G>Cā€‹(p.Glu226Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000246 in 1,614,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E226K) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.00049 ( 0 hom., cov: 32)
Exomes š‘“: 0.00022 ( 1 hom. )

Consequence

IL17RA
ENST00000319363.11 missense

Scores

2
5
12

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.01
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.056493193).
BP6
Variant 22-17102216-G-C is Benign according to our data. Variant chr22-17102216-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 340579.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000493 (75/152172) while in subpopulation AMR AF= 0.00301 (46/15274). AF 95% confidence interval is 0.00232. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL17RANM_014339.7 linkuse as main transcriptc.676G>C p.Glu226Gln missense_variant 7/13 ENST00000319363.11 NP_055154.3
IL17RANM_001289905.2 linkuse as main transcriptc.676G>C p.Glu226Gln missense_variant 7/12 NP_001276834.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL17RAENST00000319363.11 linkuse as main transcriptc.676G>C p.Glu226Gln missense_variant 7/131 NM_014339.7 ENSP00000320936 P2Q96F46-1

Frequencies

GnomAD3 genomes
AF:
0.000493
AC:
75
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
Gnomad ASJ
AF:
0.00662
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000382
AC:
96
AN:
251488
Hom.:
0
AF XY:
0.000338
AC XY:
46
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.00605
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000814
GnomAD4 exome
AF:
0.000220
AC:
322
AN:
1461880
Hom.:
1
Cov.:
33
AF XY:
0.000215
AC XY:
156
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000805
Gnomad4 ASJ exome
AF:
0.00769
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000459
Gnomad4 OTH exome
AF:
0.000546
GnomAD4 genome
AF:
0.000493
AC:
75
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.000673
AC XY:
50
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00301
Gnomad4 ASJ
AF:
0.00662
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000552
Hom.:
0
Bravo
AF:
0.000722
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.000272
AC:
33
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Immunodeficiency 51 Uncertain:1Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 12, 2024- -
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0082
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
0.84
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.20
Sift
Benign
0.20
T;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.63
MVP
0.43
MPC
0.71
ClinPred
0.12
T
GERP RS
5.2
Varity_R
0.51
gMVP
0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144085995; hg19: chr22-17583106; API