rs2272127

Variant names:

• chr2-102423413-C-A
• rs2272127
• NM_001393487.1:c.70+66C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-102423413-C-A
• chr2-102423413-C-G
• chr2-102423413-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003853.4(IL18RAP):​c.70+66C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000902 in 1,109,134 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 9.0e-7 (0 hom.)
• Consequence: IL18RAP NM_003853.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	NM_001393487.1	MANE Select	c.70+66C>A		intron	N/A	NP_001380416.1
	IL18RAP	NM_001393486.1		c.70+66C>A		intron	N/A	NP_001380415.1
	IL18RAP	NM_003853.4		c.70+66C>A		intron	N/A	NP_003844.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18RAP	ENST00000687160.1	MANE Select	c.70+66C>A		intron	N/A	ENSP00000510345.1
	IL18RAP	ENST00000264260.6	TSL:1	c.70+66C>A		intron	N/A	ENSP00000264260.2
	IL18RAP	ENST00000409369.1	TSL:1	c.-32+66C>A		intron	N/A	ENSP00000387201.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.02e-7 AC: 1 AN: 1109134 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 568486

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26420

American (AMR) AF: 0.00 AC: 0 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23798

East Asian (EAS) AF: 0.00 AC: 0 AN: 38046

South Asian (SAS) AF: 0.00 AC: 0 AN: 79100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 790520

Other (OTH) AF: 0.00 AC: 0 AN: 48836

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.34
PhyloP100		-0.48
PromoterAI		-0.0017	Neutral

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: rs2272127; hg19: chr2-103039873;