chr3-53864925-A-G

Position:

• chr3-53864925-A-G

Variant summary

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

The NM_018725.4(IL17RB):​c.1126A>G​(p.Met376Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IL17RB NM_018725.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.678

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=0.09926835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL17RB	NM_018725.4	c.1126A>G	p.Met376Val	missense_variant	11/11	ENST00000288167.8	NP_061195.2
ACTR8	XM_005265587.6	c.*140T>C		3_prime_UTR_variant	14/14		XP_005265644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL17RB	ENST00000288167.8	c.1126A>G	p.Met376Val	missense_variant	11/11	1	NM_018725.4	ENSP00000288167	P1
IL17RB	ENST00000475124.1	n.2159A>G		non_coding_transcript_exon_variant	10/10	2
IL17RB	ENST00000494338.1			downstream_gene_variant		5		ENSP00000418638

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2022

The c.1126A>G (p.M376V) alteration is located in exon 11 (coding exon 11) of the IL17RB gene. This alteration results from a A to G substitution at nucleotide position 1126, causing the methionine (M) at amino acid position 376 to be replaced by a valine (V). 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	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.92	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.061
Sift	Benign	0.60	T
Sift4G	Benign	0.38	T
Polyphen		0.022	B
Vest4		0.19
MutPred		0.49		Loss of disorder (P = 0.1571);
MVP		0.15
MPC		0.080
ClinPred		0.12	T
GERP RS		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.052
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-53898952;