chr3-53849695-C-G

Variant names:

• chr3-53849695-C-G
• rs1025689
• NM_018725.4:c.126C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018725.4(IL17RB):​c.126C>G​(p.Pro42Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 1,611,478 control chromosomes in the GnomAD database, including 297,217 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 0.48 (20701 hom., cov: 29)
  • Exomes 𝑓: 0.61 (276516 hom.)
• Consequence: IL17RB NM_018725.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 33 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.703 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RB	NM_018725.4	MANE Select	c.126C>G	p.Pro42Pro	synonymous	Exon 3 of 11	NP_061195.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL17RB	ENST00000288167.8	TSL:1 MANE Select	c.126C>G	p.Pro42Pro	synonymous	Exon 3 of 11	ENSP00000288167.3
	IL17RB	ENST00000494338.1	TSL:5	c.126C>G	p.Pro42Pro	synonymous	Exon 3 of 10	ENSP00000418638.1
	IL17RB	ENST00000475124.1	TSL:2	n.131C>G		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72848 AN: 151544 Hom.: 20701 Cov.: 29

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.520

GnomAD2 exomes AF: 0.563 AC: 140809 AN: 249936 AF XY: 0.578

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.588

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.596

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.571

GnomAD4 exome AF: 0.609 AC: 889579 AN: 1459816 Hom.: 276516 Cov.: 37 AF XY: 0.612 AC XY: 444140 AN XY: 726130

African (AFR) AF: 0.143 AC: 4767 AN: 33434

American (AMR) AF: 0.489 AC: 21763 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 15365 AN: 26100

East Asian (EAS) AF: 0.510 AC: 20204 AN: 39620

South Asian (SAS) AF: 0.617 AC: 52942 AN: 85850

European-Finnish (FIN) AF: 0.601 AC: 32061 AN: 53380

Middle Eastern (MID) AF: 0.536 AC: 3062 AN: 5712

European-Non Finnish (NFE) AF: 0.634 AC: 704813 AN: 1110898

Other (OTH) AF: 0.574 AC: 34602 AN: 60304

GnomAD4 genome AF: 0.480 AC: 72859 AN: 151662 Hom.: 20701 Cov.: 29 AF XY: 0.482 AC XY: 35697 AN XY: 74092

African (AFR) AF: 0.160 AC: 6630 AN: 41370

American (AMR) AF: 0.500 AC: 7624 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2012 AN: 3460

East Asian (EAS) AF: 0.481 AC: 2472 AN: 5134

South Asian (SAS) AF: 0.607 AC: 2917 AN: 4802

European-Finnish (FIN) AF: 0.589 AC: 6173 AN: 10486

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.636 AC: 43198 AN: 67874

Other (OTH) AF: 0.519 AC: 1088 AN: 2096

Alfa AF: 0.567 Hom.: 7260

Bravo AF: 0.456

Asia WGS AF: 0.477 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.41
DANN	Benign	0.47
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1025689; hg19: chr3-53883722; COSMIC: COSV55472502; COSMIC: COSV55472502;