3-53855822-T-C

Variant names:

• chr3-53855822-T-C
• rs999514
• NM_018725.4:c.529+481T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018725.4(IL17RB):​c.529+481T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,076 control chromosomes in the GnomAD database, including 20,462 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (20462 hom., cov: 32)
• Consequence: IL17RB NM_018725.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL17RB	NM_018725.4	c.529+481T>C		intron_variant	Intron 6 of 10	ENST00000288167.8	NP_061195.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL17RB	ENST00000288167.8	c.529+481T>C		intron_variant	Intron 6 of 10	1	NM_018725.4	ENSP00000288167.3
IL17RB	ENST00000494338.1	c.482-1022T>C		intron_variant	Intron 5 of 9	5		ENSP00000418638.1
IL17RB	ENST00000475124.1	n.534+481T>C		intron_variant	Intron 6 of 9	2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75852 AN: 151958 Hom.: 20426 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.465

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.499 AC: 75938 AN: 152076 Hom.: 20462 Cov.: 32 AF XY: 0.506 AC XY: 37587 AN XY: 74350

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.948

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.394

Gnomad4 OTH AF: 0.468

Alfa AF: 0.419 Hom.: 26589

Bravo AF: 0.518

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.6
DANN	Benign	0.27

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: rs999514; hg19: chr3-53889849;