2-102424707-T-C

Position:

• chr2-102424707-T-C

Variant summary

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

The NM_001393487.1(IL18RAP):​c.579+293T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,108 control chromosomes in the GnomAD database, including 6,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.27 (6354 hom., cov: 32)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.486

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.579+293T>C		intron_variant		ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.579+293T>C		intron_variant			NM_001393487.1	ENSP00000510345	P1
IL18RAP	ENST00000264260.6	c.579+293T>C		intron_variant		1		ENSP00000264260	P1
IL18RAP	ENST00000409369.1	c.153+293T>C		intron_variant		1		ENSP00000387201

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41523 AN: 151990 Hom.: 6349 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.273 AC: 41554 AN: 152108 Hom.: 6354 Cov.: 32 AF XY: 0.273 AC XY: 20295 AN XY: 74366

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.283

Alfa AF: 0.331 Hom.: 1727

Bravo AF: 0.279

Asia WGS AF: 0.361 AC: 1255 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.62

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: rs887971; hg19: chr2-103041167;