chr2-102438307-G-A

Variant names:

• chr2-102438307-G-A
• rs11465699
• NM_001393487.1:c.730+945G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001393487.1(IL18RAP):​c.730+945G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 152,272 control chromosomes in the GnomAD database, including 60 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 0.025 (60 hom., cov: 33)
• Consequence: IL18RAP NM_001393487.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 13 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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0246 (3753/152272) while in subpopulation NFE AF = 0.0405 (2756/68016). AF 95% confidence interval is 0.0393. There are 60 homozygotes in GnomAd4. There are 1720 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18RAP	NM_001393487.1	c.730+945G>A		intron_variant	Intron 4 of 9	ENST00000687160.1	NP_001380416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18RAP	ENST00000687160.1	c.730+945G>A		intron_variant	Intron 4 of 9		NM_001393487.1	ENSP00000510345.1
IL18RAP	ENST00000264260.6	c.730+945G>A		intron_variant	Intron 6 of 11	1		ENSP00000264260.2
IL18RAP	ENST00000409369.1	c.304+945G>A		intron_variant	Intron 4 of 9	1		ENSP00000387201.1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3753 AN: 152154 Hom.: 60 Cov.: 33

Gnomad AFR AF: 0.00763

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0255

Gnomad FIN AF: 0.00990

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0405

Gnomad OTH AF: 0.0278

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

GnomAD4 genome AF: 0.0246 AC: 3753 AN: 152272 Hom.: 60 Cov.: 33 AF XY: 0.0231 AC XY: 1720 AN XY: 74446

African (AFR) AF: 0.00760 AC: 316 AN: 41552

American (AMR) AF: 0.0155 AC: 237 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0255 AC: 123 AN: 4826

European-Finnish (FIN) AF: 0.00990 AC: 105 AN: 10608

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0405 AC: 2756 AN: 68016

Other (OTH) AF: 0.0280 AC: 59 AN: 2110

Alfa AF: 0.0282 Hom.: 55

Bravo AF: 0.0241

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		0.027
Mutation Taster		=100/0	polymorphism

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: rs11465699; hg19: chr2-103054767;