Variant 3-53849715-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018725.4(IL17RB):c.146G>A(p.Arg49Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000655 in 1,613,216 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0026 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

IL17RB
NM_018725.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.745

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045233965).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RB	NM_018725.4 link	c.146G>A	p.Arg49Gln	missense_variant	Exon 3 of 11	ENST00000288167.8	NP_061195.2	Q9NRM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IL17RB	ENST00000288167.8 link	c.146G>A	p.Arg49Gln	missense_variant	Exon 3 of 11	1	NM_018725.4	ENSP00000288167.3	Q9NRM6-1
IL17RB	ENST00000494338.1 link	c.146G>A	p.Arg49Gln	missense_variant	Exon 3 of 10	5		ENSP00000418638.1	C9IZN0
IL17RB	ENST00000475124.1 link	n.151G>A		non_coding_transcript_exon_variant	Exon 3 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

393

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00839

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.000826

AC:

207

AN:

250746

Hom.:

AF XY:

0.000649

AC XY:

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00887

Gnomad AMR exome

AF:

0.000554

Gnomad ASJ exome

AF:

0.00248

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000454

AC:

664

AN:

1461062

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

323

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.00717

Gnomad4 AMR exome

AF:

0.000717

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000228

Gnomad4 OTH exome

AF:

0.000895

GnomAD4 genome

AF:

0.00258

AC:

393

AN:

152154

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00836

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.000692

Hom.:

Bravo

AF:

0.00266

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000947

AC:

115

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000219

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Uncertain:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.1

DANN

Benign

0.73

DEOGEN2

Benign

0.036

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.67

N;.

PrimateAI

Benign

0.19

PROVEAN

Benign

0.64

N;N

REVEL

Benign

0.016

Sift

Benign

0.98

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.070

B;.

Vest4

0.056

MVP

0.067

MPC

0.077

ClinPred

0.0025

GERP RS

-3.9

Varity_R

0.015

gMVP

0.19

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