Variant 3-53858737-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018725.4(IL17RB):c.766A>G(p.Thr256Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,788 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IL17RB
NM_018725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

IL17RB (HGNC:18015): (interleukin 17 receptor B) The protein encoded by this gene is a cytokine receptor. This receptor specifically binds to IL17B and IL17E, but does not bind to IL17 and IL17C. This receptor has been shown to mediate the activation of NF-kappaB and the production of IL8 induced by IL17E. The expression of the rat counterpart of this gene was found to be significantly up-regulated during intestinal inflammation, which suggested the immunoregulatory activity of this receptor. [provided by RefSeq, Jul 2008]

IL17RB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21821862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RB	NM_018725.4 link	c.766A>G	p.Thr256Ala	missense_variant	9/11	ENST00000288167.8	NP_061195.2	Q9NRM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17RB	ENST00000288167.8 link	c.766A>G	p.Thr256Ala	missense_variant	9/11	1	NM_018725.4	ENSP00000288167.3	Q9NRM6-1
IL17RB	ENST00000494338.1 link	c.718A>G	p.Thr240Ala	missense_variant	8/10	5		ENSP00000418638.1	C9IZN0
IL17RB	ENST00000475124.1 link	n.1799A>G		non_coding_transcript_exon_variant	8/10	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727198

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 25, 2023

The c.766A>G (p.T256A) alteration is located in exon 9 (coding exon 9) of the IL17RB gene. This alteration results from a A to G substitution at nucleotide position 766, causing the threonine (T) at amino acid position 256 to be replaced by an alanine (A). 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

0.069

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.67

N;N

REVEL

Benign

0.17

Sift

Benign

0.19

T;T

Sift4G

Uncertain

0.024

D;D

Polyphen

0.78

P;.

Vest4

0.11

MutPred

0.20

Loss of glycosylation at T256 (P = 0.045);.;

MVP

0.23

MPC

0.068

ClinPred

0.61

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.57

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over