rs1420100

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IL18RAP	NM_001393486.1	c.-101+745C>A		intron_variant			NP_001380415.1
IL18RAP	NM_001393488.1	c.-731+745C>A		intron_variant			NP_001380417.1
IL18RAP	NM_001393489.1	c.-202+745C>A		intron_variant			NP_001380418.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000264260.6	c.-101+745C>A		intron_variant		1		ENSP00000264260	P1
IL18RAP	ENST00000409369.1	c.-202+745C>A		intron_variant		1		ENSP00000387201
IL18RAP	ENST00000450855.1	c.-101+745C>A		intron_variant		4		ENSP00000389815

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

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.522

Alfa AF: 0.408 Hom.: 1496

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1420100; hg19: chr2-103037002; COSMIC: COSV51824637; COSMIC: COSV51824637;