Variant 22-49998060-G-A 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_001371417.1(IL17REL):c.1000C>T(p.Pro334Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,593,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL17REL
NM_001371417.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.361

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 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=0.050201386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IL17REL	NM_001371417.1 linkuse as main transcript	c.1000C>T	p.Pro334Ser	missense_variant	11/15	ENST00000695950.1
IL17REL	NM_001371416.1 linkuse as main transcript	c.1000C>T	p.Pro334Ser	missense_variant	11/15
IL17REL	NM_001001694.3 linkuse as main transcript	c.784C>T	p.Pro262Ser	missense_variant	11/15
IL17REL	XR_001755245.2 linkuse as main transcript	n.1119C>T		non_coding_transcript_exon_variant	11/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IL17REL	ENST00000695950.1 linkuse as main transcript	c.1000C>T	p.Pro334Ser	missense_variant	11/15		NM_001371417.1	A2
IL17REL	ENST00000695951.1 linkuse as main transcript	c.1000C>T	p.Pro334Ser	missense_variant	11/15			P2
IL17REL	ENST00000389983.7 linkuse as main transcript	c.*919C>T		3_prime_UTR_variant, NMD_transcript_variant	11/15	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.00000443

AC:

AN:

225764

Hom.:

AF XY:

0.00

AC XY:

AN XY:

123734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000361

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1441114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000266

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:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

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 22, 2021

The c.784C>T (p.P262S) alteration is located in exon 11 (coding exon 8) of the IL17REL gene. This alteration results from a C to T substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 to be replaced by a serine (S). 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

0.092

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

Cadd

Benign

7.9

Dann

Benign

0.94

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.46

T;.

M_CAP

Benign

0.0025

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.034

Sift

Benign

0.21

T;T

Sift4G

Benign

0.93

T;T

Polyphen

0.050

B;B

Vest4

0.12

MutPred

0.42

Gain of sheet (P = 0.039);Gain of sheet (P = 0.039);

MVP

0.099

MPC

0.26

ClinPred

0.053

GERP RS

0.22

Varity_R

0.090

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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