22-49999501-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001371417.1(IL17REL):c.692T>A(p.Val231Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IL17REL NM_001371417.1 missense, splice_region
• Scores: Splicing: ADA: 0.01525
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.294

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17REL	NM_001371417.1	c.692T>A	p.Val231Glu	missense_variant, splice_region_variant	8/15	ENST00000695950.1
IL17REL	NM_001371416.1	c.692T>A	p.Val231Glu	missense_variant, splice_region_variant	8/15
IL17REL	NM_001001694.3	c.476T>A	p.Val159Glu	missense_variant, splice_region_variant	8/15
IL17REL	XR_001755245.2	n.811T>A		splice_region_variant, non_coding_transcript_exon_variant	8/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17REL	ENST00000695950.1	c.692T>A	p.Val231Glu	missense_variant, splice_region_variant	8/15		NM_001371417.1	A2
IL17REL	ENST00000695951.1	c.692T>A	p.Val231Glu	missense_variant, splice_region_variant	8/15			P2
IL17REL	ENST00000389983.7	c.*611T>A		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	8/15	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.476T>A (p.V159E) alteration is located in exon 8 (coding exon 5) of the IL17REL gene. This alteration results from a T to A substitution at nucleotide position 476, causing the valine (V) at amino acid position 159 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T
Eigen	Benign	-0.059
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.44	T;.
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.57
MutPred		0.46		Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);
MVP		0.16
MPC		0.53
ClinPred		0.54	D
GERP RS		2.4
Varity_R		0.36
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.015
dbscSNV1_RF	Benign	0.15
SpliceAI score (max)		0.16		Details are displayed if max score is > 0.2

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: chr22-50437930;