Variant 22-49998062-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001371417.1(IL17REL):c.998A>G(p.Tyr333Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,442,780 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

IL17REL
NM_001371417.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.492

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17REL	NM_001371417.1 linkuse as main transcript	c.998A>G	p.Tyr333Cys	missense_variant	11/15	ENST00000695950.1	NP_001358346.1
IL17REL	NM_001371416.1 linkuse as main transcript	c.998A>G	p.Tyr333Cys	missense_variant	11/15		NP_001358345.1
IL17REL	NM_001001694.3 linkuse as main transcript	c.782A>G	p.Tyr261Cys	missense_variant	11/15		NP_001001694.2	Q6ZVW7
IL17REL	XR_001755245.2 linkuse as main transcript	n.1117A>G		non_coding_transcript_exon_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17REL	ENST00000695950.1 linkuse as main transcript	c.998A>G	p.Tyr333Cys	missense_variant	11/15		NM_001371417.1	ENSP00000512282.1	A0A8Q3WKV1
IL17REL	ENST00000695951.1 linkuse as main transcript	c.998A>G	p.Tyr333Cys	missense_variant	11/15			ENSP00000512283.1	A0A8Q3WLX3
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*917A>G		non_coding_transcript_exon_variant	11/15	2		ENSP00000374633.3	Q6ZVW7
IL17REL	ENST00000389983.7 linkuse as main transcript	n.*917A>G		3_prime_UTR_variant	11/15	2		ENSP00000374633.3	Q6ZVW7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000439

AC:

AN:

227860

Hom.:

AF XY:

0.00000801

AC XY:

AN XY:

124904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000352

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1442780

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000712

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Oct 09, 2024

The c.782A>G (p.Y261C) alteration is located in exon 11 (coding exon 8) of the IL17REL gene. This alteration results from a A to G substitution at nucleotide position 782, causing the tyrosine (Y) at amino acid position 261 to be replaced by a cysteine (C). 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

0.97

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Benign

0.10

Eigen_PC

Benign

-0.031

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.65

T;.

M_CAP

Benign

0.0069

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-6.2

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.60

MutPred

0.53

Gain of disorder (P = 0.0152);Gain of disorder (P = 0.0152);

MVP

0.24

MPC

0.93

ClinPred

0.99

GERP RS

2.4

Varity_R

0.55

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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