22-49997075-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_001371417.1(IL17REL):​c.1258-1G>A variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

IL17REL
NM_001371417.1 splice_acceptor, intron

Scores

1
6
Splicing: ADA: 1.000
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78
Variant links:
Genes affected
IL17REL (HGNC:33808): (interleukin 17 receptor E like) Predicted to enable interleukin-17 receptor activity. Predicted to be involved in cytokine-mediated signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.053149607 fraction of the gene. Cryptic splice site detected, with MaxEntScore 7.4, offset of 1, new splice context is: cctgccctcccccacccaAGgtg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IL17RELNM_001371417.1 linkc.1258-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 ENST00000695950.1 NP_001358346.1
IL17RELNM_001371416.1 linkc.1191-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 NP_001358345.1
IL17RELNM_001001694.3 linkc.975-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 NP_001001694.2 Q6ZVW7
IL17RELXR_001755245.2 linkn.1377-1G>A splice_acceptor_variant, intron_variant Intron 13 of 15

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IL17RELENST00000695950.1 linkc.1258-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 NM_001371417.1 ENSP00000512282.1 A0A8Q3WKV1
IL17RELENST00000695951.1 linkc.1191-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 ENSP00000512283.1 A0A8Q3WLX3
IL17RELENST00000389983.7 linkn.*1110-1G>A splice_acceptor_variant, intron_variant Intron 13 of 14 2 ENSP00000374633.3 Q6ZVW7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1418076
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
703038
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Feb 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

IL17REL: PM2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Benign
0.96
Eigen
Uncertain
0.40
Eigen_PC
Benign
0.058
FATHMM_MKL
Benign
0.094
N
GERP RS
1.6

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.92
SpliceAI score (max)
0.76
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.62
Position offset: -2
DS_AL_spliceai
0.76
Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50435504; API