rs1043261

Positions:

• chr3-53865249-C-A
• chr3-53865249-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018725.4(IL17RB):​c.1450C>A​(p.Gln484Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL17RB NM_018725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08563492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RB	NM_018725.4	c.1450C>A	p.Gln484Lys	missense_variant	11/11	ENST00000288167.8	NP_061195.2
ACTR8	XM_005265587.6	c.*46-230G>T		intron_variant			XP_005265644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RB	ENST00000288167.8	c.1450C>A	p.Gln484Lys	missense_variant	11/11	1	NM_018725.4	ENSP00000288167	P1
IL17RB	ENST00000475124.1	n.2483C>A		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.037
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.44	B
Vest4		0.20
MutPred		0.37		Gain of solvent accessibility (P = 0.0039);
MVP		0.24
MPC		0.11
ClinPred		0.33	T
GERP RS		2.9
Varity_R		0.19
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1043261; hg19: chr3-53899276;