Variant chr22-49997383-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001371416.1(IL17REL):c.1127G>A(p.Gly376Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

IL17REL
NM_001371416.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.88

Variant links:

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 links:

IL17REL (HGNC:):

IL17REL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03744763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17REL	NM_001371417.1 linkuse as main transcript	c.1194G>A	p.Arg398Arg	synonymous_variant	13/15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1 linkuse as main transcript	c.1127G>A	p.Gly376Glu	missense_variant	13/15		NP_001358345.1
IL17REL	NM_001001694.3 linkuse as main transcript	c.911G>A	p.Gly304Glu	missense_variant	13/15		NP_001001694.2	Q6ZVW7
IL17REL	XR_001755245.2 linkuse as main transcript	n.1313G>A		non_coding_transcript_exon_variant	13/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17REL	ENST00000695950.1 linkuse as main transcript	c.1194G>A	p.Arg398Arg	synonymous_variant	13/15		NM_001371417.1	ENSP00000512282.1	A0A8Q3WKV1
IL17REL	ENST00000695951.1 linkuse as main transcript	c.1127G>A	p.Gly376Glu	missense_variant	13/15			ENSP00000512283.1	A0A8Q3WLX3
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*1046G>A		non_coding_transcript_exon_variant	13/15	2		ENSP00000374633.3	Q6ZVW7
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*1046G>A		3_prime_UTR_variant	13/15	2		ENSP00000374633.3	Q6ZVW7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.911G>A (p.G304E) 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 911, causing the glycine (G) at amino acid position 304 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

Benign

0.073

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.44

DANN

Benign

0.54

DEOGEN2

Benign

0.00045

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.31

T;.

M_CAP

Benign

0.0013

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.20

N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.0040

Sift

Uncertain

0.013

D;D

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.093

MutPred

0.15

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.040

MPC

0.28

ClinPred

0.089

GERP RS

-2.9

Varity_R

0.041

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over