22-49997719-C-A

Position:

• chr22-49997719-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001371417.1(IL17REL):​c.1059G>T​(p.Trp353Cys) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL17REL NM_001371417.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.229

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]

IL17REL (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33435583).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17REL	NM_001371417.1	c.1059G>T	p.Trp353Cys	missense_variant	12/15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1	c.1059G>T	p.Trp353Cys	missense_variant	12/15		NP_001358345.1
IL17REL	NM_001001694.3	c.843G>T	p.Trp281Cys	missense_variant	12/15		NP_001001694.2
IL17REL	XR_001755245.2	n.1178G>T		non_coding_transcript_exon_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17REL	ENST00000695950.1	c.1059G>T	p.Trp353Cys	missense_variant	12/15		NM_001371417.1	ENSP00000512282.1
IL17REL	ENST00000695951.1	c.1059G>T	p.Trp353Cys	missense_variant	12/15			ENSP00000512283.1
IL17REL	ENST00000389983.7	n.*978G>T		non_coding_transcript_exon_variant	12/15	2		ENSP00000374633.3
IL17REL	ENST00000389983.7	n.*978G>T		3_prime_UTR_variant	12/15	2		ENSP00000374633.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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 08, 2024

The c.843G>T (p.W281C) alteration is located in exon 12 (coding exon 9) of the IL17REL gene. This alteration results from a G to T substitution at nucleotide position 843, causing the tryptophan (W) at amino acid position 281 to be replaced by a cysteine (C). 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	Pathogenic	0.80
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.54	T;.
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Benign	0.057
Sift	Uncertain	0.018	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.99	D;D
Vest4		0.34
MutPred		0.51		Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP		0.072
MPC		0.88
ClinPred		0.96	D
GERP RS		2.2
Varity_R		0.30
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr22-50436148;