rs116821431

Variant names:

• chr3-53849715-G-A
• rs116821431
• NM_018725.4:c.146G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.745
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045233965).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018725.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RB	NM_018725.4	MANE Select	c.146G>A	p.Arg49Gln	missense	Exon 3 of 11	NP_061195.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RB	ENST00000288167.8	TSL:1 MANE Select	c.146G>A	p.Arg49Gln	missense	Exon 3 of 11	ENSP00000288167.3	Q9NRM6-1
	IL17RB	ENST00000899729.1		c.146G>A	p.Arg49Gln	missense	Exon 3 of 13	ENSP00000569788.1
	IL17RB	ENST00000899731.1		c.146G>A	p.Arg49Gln	missense	Exon 3 of 12	ENSP00000569790.1

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 393 AN: 152036 Hom.: 2 Cov.: 31

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

GnomAD2 exomes AF: 0.000826 AC: 207 AN: 250746 AF XY: 0.000649

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 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.: 2 Cov.: 32 AF XY: 0.000444 AC XY: 323 AN XY: 726810

African (AFR) AF: 0.00717 AC: 240 AN: 33460

American (AMR) AF: 0.000717 AC: 32 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00249 AC: 65 AN: 26118

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39672

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5748

European-Non Finnish (NFE) AF: 0.000228 AC: 254 AN: 1111598

Other (OTH) AF: 0.000895 AC: 54 AN: 60350

GnomAD4 genome AF: 0.00258 AC: 393 AN: 152154 Hom.: 2 Cov.: 31 AF XY: 0.00246 AC XY: 183 AN XY: 74400

African (AFR) AF: 0.00836 AC: 347 AN: 41484

American (AMR) AF: 0.000719 AC: 11 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00518 AC: 18 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67992

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00266

ESP6500AA AF: 0.00613 AC: 27

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000947 AC: 115

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000219

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.65	T
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	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.67	N
PhyloP100		-0.74
PrimateAI	Benign	0.19	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.016
Sift	Benign	0.98	T
Sift4G	Benign	0.40	T
Polyphen		0.070	B
Vest4		0.056
MVP		0.067
MPC		0.077
ClinPred		0.0025	T
GERP RS		-3.9
Varity_R		0.015
gMVP		0.19
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs116821431; hg19: chr3-53883742; COSMIC: COSV99861104; COSMIC: COSV99861104;