rs1420100

Variant names:

• chr2-102420542-C-A
• rs1420100
• ENST00000264260.6:c.-101+745C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102420542-C-A
• chr2-102420542-C-G
• chr2-102420542-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264260.6(IL18RAP):​c.-101+745C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,954 control chromosomes in the GnomAD database, including 23,611 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 0.54 (23611 hom., cov: 32)
• Consequence: IL18RAP ENST00000264260.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 16 publications found

Genes affected

IL18RAP (HGNC:5989): (interleukin 18 receptor accessory protein) The protein encoded by this gene is an accessory subunit of the heterodimeric receptor for interleukin 18 (IL18), a proinflammatory cytokine involved in inducing cell-mediated immunity. This protein enhances the IL18-binding activity of the IL18 receptor and plays a role in signaling by IL18. Mutations in this gene are associated with Crohn's disease and inflammatory bowel disease, and susceptibility to celiac disease and leprosy. Alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393486.1	c.-101+745C>A		intron_variant	Intron 3 of 12		NP_001380415.1
IL18RAP	NM_003853.4	c.-101+745C>A		intron_variant	Intron 2 of 11		NP_003844.1
IL18RAP	NM_001393488.1	c.-731+745C>A		intron_variant	Intron 2 of 11		NP_001380417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6	c.-101+745C>A		intron_variant	Intron 2 of 11	1		ENSP00000264260.2
IL18RAP	ENST00000409369.1	c.-202+745C>A		intron_variant	Intron 1 of 9	1		ENSP00000387201.1
IL18RAP	ENST00000450855.1	c.-101+745C>A		intron_variant	Intron 1 of 2	4		ENSP00000389815.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81218 AN: 151836 Hom.: 23579 Cov.: 32

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.535 AC: 81303 AN: 151954 Hom.: 23611 Cov.: 32 AF XY: 0.529 AC XY: 39282 AN XY: 74272

African (AFR) AF: 0.733 AC: 30343 AN: 41398

American (AMR) AF: 0.414 AC: 6314 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2131 AN: 3470

East Asian (EAS) AF: 0.150 AC: 774 AN: 5176

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4816

European-Finnish (FIN) AF: 0.542 AC: 5725 AN: 10564

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33032 AN: 67952

Other (OTH) AF: 0.522 AC: 1100 AN: 2108

Alfa AF: 0.455 Hom.: 2436

Bravo AF: 0.536

Asia WGS AF: 0.234 AC: 814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.47
PhyloP100		-0.59
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: rs1420100; hg19: chr2-103037002; COSMIC: COSV51824637; COSMIC: COSV51824637;