NM_018725.4:c.1078A>G

Variant names:

• chr3-53864877-A-G
• NM_018725.4:c.1078A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018725.4(IL17RB):​c.1078A>G​(p.Arg360Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RB NM_018725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 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]

ACTR8 (HGNC:14672): (actin related protein 8) Predicted to enable ATP binding activity. Predicted to be involved in chromatin remodeling; double-strand break repair; and regulation of transcription, DNA-templated. Located in centrosome and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21385509).

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.1078A>G	p.Arg360Gly	missense	Exon 11 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.1078A>G	p.Arg360Gly	missense	Exon 11 of 11	ENSP00000288167.3	Q9NRM6-1
	IL17RB	ENST00000899729.1		c.1339A>G	p.Arg447Gly	missense	Exon 13 of 13	ENSP00000569788.1
	IL17RB	ENST00000899731.1		c.1252A>G	p.Arg418Gly	missense	Exon 12 of 12	ENSP00000569790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.55		Loss of catalytic residue at R360 (P = 0.0171)
MVP		0.27
MPC		0.13
ClinPred		0.66	D
GERP RS		4.6
Varity_R		0.15
gMVP		0.25
Mutation Taster		=77/23	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

hg19: chr3-53898904;