chr22-49999324-C-T

Position:

• chr22-49999324-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371417.1(IL17REL):​c.784G>A​(p.Ala262Thr) 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: 31)
• Consequence: IL17REL NM_001371417.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0250

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25486076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17REL	NM_001371417.1	c.784G>A	p.Ala262Thr	missense_variant	9/15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1	c.784G>A	p.Ala262Thr	missense_variant	9/15		NP_001358345.1
IL17REL	NM_001001694.3	c.568G>A	p.Ala190Thr	missense_variant	9/15		NP_001001694.2
IL17REL	XR_001755245.2	n.903G>A		non_coding_transcript_exon_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17REL	ENST00000695950.1	c.784G>A	p.Ala262Thr	missense_variant	9/15		NM_001371417.1	ENSP00000512282.1
IL17REL	ENST00000695951.1	c.784G>A	p.Ala262Thr	missense_variant	9/15			ENSP00000512283.1
IL17REL	ENST00000389983.7	n.*703G>A		non_coding_transcript_exon_variant	9/15	2		ENSP00000374633.3
IL17REL	ENST00000389983.7	n.*703G>A		3_prime_UTR_variant	9/15	2		ENSP00000374633.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Jul 30, 2024

The c.568G>A (p.A190T) alteration is located in exon 9 (coding exon 6) of the IL17REL gene. This alteration results from a G to A substitution at nucleotide position 568, causing the alanine (A) at amino acid position 190 to be replaced by a threonine (T). 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	Benign	0.30
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0069	T;T
Eigen	Benign	-0.099
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.61	T;.
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.11
Sift	Benign	0.65	T;T
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	D;D
Vest4		0.42
MutPred		0.34		Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.067
MPC		0.79
ClinPred		0.53	D
GERP RS		3.0
Varity_R		0.097
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs747789553; hg19: chr22-50437753;