3-53857653-T-C

Variant names:

• chr3-53857653-T-C
• NM_018725.4:c.710T>C

Variant summary

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

The NM_018725.4(IL17RB):​c.710T>C​(p.Ile237Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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: 3.62

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

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=0.14082584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RB	NM_018725.4	c.710T>C	p.Ile237Thr	missense_variant	Exon 8 of 11	ENST00000288167.8	NP_061195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RB	ENST00000288167.8	c.710T>C	p.Ile237Thr	missense_variant	Exon 8 of 11	1	NM_018725.4	ENSP00000288167.3
IL17RB	ENST00000494338.1	c.662T>C	p.Ile221Thr	missense_variant	Exon 7 of 10	5		ENSP00000418638.1
IL17RB	ENST00000475124.1	n.715T>C		non_coding_transcript_exon_variant	Exon 8 of 10	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.710T>C (p.I237T) alteration is located in exon 8 (coding exon 8) of the IL17RB gene. This alteration results from a T to C substitution at nucleotide position 710, causing the isoleucine (I) at amino acid position 237 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Benign	0.72
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.085
Sift	Benign	0.19	T;T
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.42	B;.
Vest4		0.24
MutPred		0.56		Loss of stability (P = 0.0101);.;
MVP		0.22
MPC		0.21
ClinPred		0.62	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.58
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-53891680;