rs2232337

Variant names:

• chr3-53855341-G-A
• rs2232337
• NM_018725.4:c.529G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 4P and 6B. PP3_Strong BP6_Moderate BS2

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 (★).

• 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
• Publications: 14 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: Likely_benign. The variant received -2 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• 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 VariationId is 3250527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 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.529G>A	p.Gly177Arg	missense splice_region	Exon 6 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.529G>A	p.Gly177Arg	missense splice_region	Exon 6 of 11	ENSP00000288167.3	Q9NRM6-1
	IL17RB	ENST00000899729.1		c.703G>A	p.Gly235Arg	missense splice_region	Exon 7 of 13	ENSP00000569788.1
	IL17RB	ENST00000899731.1		c.703G>A	p.Gly235Arg	missense splice_region	Exon 7 of 12	ENSP00000569790.1

Frequencies

GnomAD3 genomes AF: 0.00471 AC: 716 AN: 152132 Hom.: 4 Cov.: 32

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

GnomAD2 exomes AF: 0.00444 AC: 1098 AN: 247184 AF XY: 0.00480

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 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.: 45 Cov.: 26 AF XY: 0.00623 AC XY: 4483 AN XY: 719154

African (AFR) AF: 0.000938 AC: 31 AN: 33040

American (AMR) AF: 0.00257 AC: 114 AN: 44314

Ashkenazi Jewish (ASJ) AF: 0.00128 AC: 33 AN: 25780

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39586

South Asian (SAS) AF: 0.00766 AC: 654 AN: 85406

European-Finnish (FIN) AF: 0.00222 AC: 118 AN: 53240

Middle Eastern (MID) AF: 0.00696 AC: 40 AN: 5746

European-Non Finnish (NFE) AF: 0.00679 AC: 7441 AN: 1096522

Other (OTH) AF: 0.00587 AC: 351 AN: 59808

GnomAD4 genome AF: 0.00470 AC: 716 AN: 152250 Hom.: 4 Cov.: 32 AF XY: 0.00446 AC XY: 332 AN XY: 74450

African (AFR) AF: 0.00120 AC: 50 AN: 41534

American (AMR) AF: 0.00478 AC: 73 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.00217 AC: 23 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00726 AC: 494 AN: 68030

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00586 Hom.: 16

Bravo AF: 0.00414

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00686 AC: 59

ExAC AF: 0.00404 AC: 491

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00607

EpiControl AF: 0.00683

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.0
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.25		Gain of MoRF binding (P = 0.0264)
MVP		0.33
MPC		0.44
ClinPred		0.030	T
GERP RS		6.0
Varity_R		0.88
gMVP		0.67
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs2232337; hg19: chr3-53889368; COSMIC: COSV99071889; COSMIC: COSV99071889;