2-102438307-G-A

Position:

• chr2-102438307-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL18RAP	NM_001393487.1	c.730+945G>A		intron_variant		ENST00000687160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL18RAP	ENST00000687160.1	c.730+945G>A		intron_variant			NM_001393487.1	P1
IL18RAP	ENST00000264260.6	c.730+945G>A		intron_variant		1		P1
IL18RAP	ENST00000409369.1	c.304+945G>A		intron_variant		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

Gnomad4 AFR AF: 0.00760

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0255

Gnomad4 FIN AF: 0.00990

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.0345 Hom.: 21

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

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: rs11465699; hg19: chr2-103054767;