Variant chr3-53855341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP6_ModerateBS2

The NM_018725.4(IL17RB):c.529G>A(p.Gly177Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00596 in 1,595,692 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0047 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 45 hom. )

Consequence

IL17RB
NM_018725.4 missense, splice_region

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.95

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 Likely_benign. Variant got -5 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 9: AlphaMissense, Cadd, Dann, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen, FATHMM_MKL, PROVEAN [when BayesDel_addAF, BayesDel_noAF, M_CAP, MetaRNN, MutationTaster, PrimateAI, REVEL was below the threshold]

BP6

Variant 3-53855341-G-A is Benign according to our data. Variant chr3-53855341-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3250527.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RB	NM_018725.4 link	c.529G>A	p.Gly177Arg	missense_variant, splice_region_variant	6/11	ENST00000288167.8	NP_061195.2	Q9NRM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IL17RB	ENST00000288167.8 link	c.529G>A	p.Gly177Arg	missense_variant, splice_region_variant	6/11	1	NM_018725.4	ENSP00000288167.3	Q9NRM6-1
IL17RB	ENST00000494338.1 link	c.482-1503G>A		intron_variant		5		ENSP00000418638.1	C9IZN0
IL17RB	ENST00000475124.1 link	n.534G>A		splice_region_variant, non_coding_transcript_exon_variant	6/10	2

Frequencies

GnomAD3 genomes

AF:

0.00471

AC:

716

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00829

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00726

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00444

AC:

1098

AN:

247184

Hom.:

AF XY:

0.00480

AC XY:

642

AN XY:

133650

show subpopulations

Gnomad AFR exome

AF:

0.00137

Gnomad AMR exome

AF:

0.00253

Gnomad ASJ exome

AF:

0.00143

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00730

Gnomad FIN exome

AF:

0.00246

Gnomad NFE exome

AF:

0.00598

Gnomad OTH exome

AF:

0.00496

GnomAD4 exome

AF:

0.00609

AC:

8787

AN:

1443442

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

4483

AN XY:

719154

show subpopulations

Gnomad4 AFR exome

AF:

0.000938

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00766

Gnomad4 FIN exome

AF:

0.00222

Gnomad4 NFE exome

AF:

0.00679

Gnomad4 OTH exome

AF:

0.00587

GnomAD4 genome

AF:

0.00470

AC:

716

AN:

152250

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

332

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00478

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.00217

Gnomad4 NFE

AF:

0.00726

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00617

Hom.:

Bravo

AF:

0.00414

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00404

AC:

491

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00607

EpiControl

AF:

0.00683

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

IL17RB: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.84

M_CAP

Benign

0.0085

MetaRNN

Benign

0.0093

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.20

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.042

Polyphen

1.0

Vest4

0.55

MutPred

0.25

Gain of MoRF binding (P = 0.0264);

MVP

0.33

MPC

0.44

ClinPred

0.030

GERP RS

6.0

Varity_R

0.88

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.58

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.58

Position offset: 0

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