22-49999324-C-T

Variant names:

• chr22-49999324-C-T
• rs747789553
• NM_001371417.1:c.784G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371417.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	NM_001371417.1	MANE Select	c.784G>A	p.Ala262Thr	missense	Exon 9 of 15	NP_001358346.1	Q6ZVW7-1
	IL17REL	NM_001371416.1		c.784G>A	p.Ala262Thr	missense	Exon 9 of 15	NP_001358345.1	A0A8Q3WLX3
	IL17REL	NM_001001694.3		c.568G>A	p.Ala190Thr	missense	Exon 9 of 15	NP_001001694.2	Q6ZVW7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17REL	ENST00000695950.1	MANE Select	c.784G>A	p.Ala262Thr	missense	Exon 9 of 15	ENSP00000512282.1	Q6ZVW7-1
	IL17REL	ENST00000695951.1		c.784G>A	p.Ala262Thr	missense	Exon 9 of 15	ENSP00000512283.1	A0A8Q3WLX3
	IL17REL	ENST00000389983.7	TSL:2	n.*703G>A		non_coding_transcript_exon	Exon 9 of 15	ENSP00000374633.3	A0AAA9X3B1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.025
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.11
Sift	Benign	0.65	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.34		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
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs747789553; hg19: chr22-50437753;