Variant rs201298520 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_014443.3(IL17B):c.527G>A(p.Cys176Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000285 in 1,578,804 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 (no stars).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

IL17B
NM_014443.3 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

IL17B (HGNC:5982): (interleukin 17B) The protein encoded by this gene is a T cell-derived cytokine that shares sequence similarity with IL17. This cytokine was reported to stimulate the release of TNF alpha (TNF) and IL1 beta (IL1B) from a monocytic cell line. Immunohistochemical analysis of several nerve tissues indicated that this cytokine is primarily localized to neuronal cell bodies. Alternative splicing results in multiple splice variants. [provided by RefSeq, Dec 2015]

IL17B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL17B	NM_014443.3 linkuse as main transcript	c.527G>A	p.Cys176Tyr	missense_variant	3/3	ENST00000261796.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IL17B	ENST00000261796.4 linkuse as main transcript	c.527G>A	p.Cys176Tyr	missense_variant	3/3	1	NM_014443.3	P1
	ENST00000521756.1 linkuse as main transcript	n.181-324C>T		intron_variant, non_coding_transcript_variant		3
IL17B	ENST00000505432.1 linkuse as main transcript	n.601G>A		non_coding_transcript_exon_variant	3/3	3
IL17B	ENST00000518814.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000434

AC:

AN:

230182

Hom.:

AF XY:

0.0000557

AC XY:

AN XY:

125782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000266

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:

0.000172

GnomAD4 exome

AF:

0.0000231

AC:

AN:

1426560

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

705690

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000296

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:

0.0000100

Gnomad4 OTH exome

AF:

0.000135

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Keratoconus 1

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Apr 21, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.86

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.54

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-11

REVEL

Pathogenic

0.85

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.96

MutPred

0.90

Loss of disorder (P = 0.004);

MVP

0.68

MPC

1.2

ClinPred

0.98

GERP RS

5.2

Varity_R

0.96

gMVP

0.95

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