Variant chr5-149374499-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014443.3(IL17B):c.413T>C(p.Met138Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,460,854 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: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

IL17B
NM_014443.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

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:

IL17B (HGNC:):

IL17B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17B	NM_014443.3 linkuse as main transcript	c.413T>C	p.Met138Thr	missense_variant	3/3	ENST00000261796.4	NP_055258.1	Q9UHF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17B	ENST00000261796.4 linkuse as main transcript	c.413T>C	p.Met138Thr	missense_variant	3/3	1	NM_014443.3	ENSP00000261796.3	Q9UHF5
IL17B	ENST00000505432.1 linkuse as main transcript	n.487T>C		non_coding_transcript_exon_variant	3/3	3
ENSG00000253865	ENST00000521756.1 linkuse as main transcript	n.181-210A>G		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

246286

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

134072

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460854

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.000109

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

Jan 31, 2022

The c.413T>C (p.M138T) alteration is located in exon 3 (coding exon 3) of the IL17B gene. This alteration results from a T to C substitution at nucleotide position 413, causing the methionine (M) at amino acid position 138 to be replaced by a threonine (T). 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

0.86

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.77

M_CAP

Benign

0.035

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.26

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

0.76

Vest4

0.69

MutPred

0.69

Gain of glycosylation at M138 (P = 0.0122);

MVP

0.82

MPC

0.49

ClinPred

0.91

GERP RS

5.2

Varity_R

0.57

gMVP

0.70

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