Variant 22-49999298-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001371417.1(IL17REL):c.810T>G(p.Phe270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IL17REL
NM_001371417.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.205

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL17REL	NM_001371417.1 linkuse as main transcript	c.810T>G	p.Phe270Leu	missense_variant	9/15	ENST00000695950.1
IL17REL	NM_001371416.1 linkuse as main transcript	c.810T>G	p.Phe270Leu	missense_variant	9/15
IL17REL	NM_001001694.3 linkuse as main transcript	c.594T>G	p.Phe198Leu	missense_variant	9/15
IL17REL	XR_001755245.2 linkuse as main transcript	n.929T>G		non_coding_transcript_exon_variant	9/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IL17REL	ENST00000695950.1 linkuse as main transcript	c.810T>G	p.Phe270Leu	missense_variant	9/15		NM_001371417.1	A2
IL17REL	ENST00000695951.1 linkuse as main transcript	c.810T>G	p.Phe270Leu	missense_variant	9/15			P2
IL17REL	ENST00000389983.7 linkuse as main transcript	c.*729T>G		3_prime_UTR_variant, NMD_transcript_variant	9/15	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460746

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726684

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jan 10, 2022

The c.594T>G (p.F198L) alteration is located in exon 9 (coding exon 6) of the IL17REL gene. This alteration results from a T to G substitution at nucleotide position 594, causing the phenylalanine (F) at amino acid position 198 to be replaced by a leucine (L). 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

0.99

BayesDel_addAF

Benign

0.00083

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.078

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.50

T;.

M_CAP

Benign

0.0094

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.95

N;N

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Benign

0.25

Sift

Benign

0.093

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.71

MutPred

0.77

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.19

MPC

0.73

ClinPred

1.0

GERP RS

-1.9

Varity_R

0.41

gMVP

0.91

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