22-49997401-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001371417.1(IL17REL):c.1176G>A(p.Gln392=) variant causes a synonymous 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IL17REL NM_001371417.1 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.231

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0705359).
• BP7: Synonymous conserved (PhyloP=0.231 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17REL	NM_001371417.1	c.1176G>A	p.Gln392=	synonymous_variant	13/15	ENST00000695950.1
IL17REL	NM_001371416.1	c.1109G>A	p.Arg370Lys	missense_variant	13/15
IL17REL	NM_001001694.3	c.893G>A	p.Arg298Lys	missense_variant	13/15
IL17REL	XR_001755245.2	n.1295G>A		non_coding_transcript_exon_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL17REL	ENST00000695950.1	c.1176G>A	p.Gln392=	synonymous_variant	13/15		NM_001371417.1	A2
IL17REL	ENST00000695951.1	c.1109G>A	p.Arg370Lys	missense_variant	13/15			P2
IL17REL	ENST00000389983.7	c.*1028G>A		3_prime_UTR_variant, NMD_transcript_variant	13/15	2

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

Oct 13, 2023

The c.893G>A (p.R298K) alteration is located in exon 13 (coding exon 10) of the IL17REL gene. This alteration results from a G to A substitution at nucleotide position 893, causing the arginine (R) at amino acid position 298 to be replaced by a lysine (K). 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	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	4.9
Dann	Benign	0.89
DEOGEN2	Benign	0.0043	T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.41	T;.
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.039
Sift	Benign	0.095	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.039	B;B
Vest4		0.25
MutPred		0.20		Gain of methylation at R298 (P = 0.0227);Gain of methylation at R298 (P = 0.0227);
MVP		0.048
MPC		0.59
ClinPred		0.40	T
GERP RS		1.4
Varity_R		0.11
gMVP		0.46

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: chr22-50435830;