NM_003855.5:c.303-1052A>G

Variant names:

• chr2-102370901-A-G
• rs7579737
• NM_003855.5:c.303-1052A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.303-1052A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,126 control chromosomes in the GnomAD database, including 6,842 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 0.29 (6842 hom., cov: 33)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.961
• Publications: 15 publications found

Genes affected

IL18R1 (HGNC:5988): (interleukin 18 receptor 1) The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This receptor specifically binds interleukin 18 (IL18), and is essential for IL18 mediated signal transduction. IFN-alpha and IL12 are reported to induce the expression of this receptor in NK and T cells. This gene along with four other members of the interleukin 1 receptor family, including IL1R2, IL1R1, ILRL2 (IL-1Rrp2), and IL1RL1 (T1/ST2), form a gene cluster on chromosome 2q. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	NM_003855.5	MANE Select	c.303-1052A>G		intron	N/A	NP_003846.1	Q13478
	IL18R1	NM_001371418.1		c.303-1052A>G		intron	N/A	NP_001358347.1	B7ZKV7
	IL18R1	NM_001371419.1		c.303-1052A>G		intron	N/A	NP_001358348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL18R1	ENST00000233957.7	TSL:5 MANE Select	c.303-1052A>G		intron	N/A	ENSP00000233957.1	Q13478
	IL18R1	ENST00000409599.5	TSL:5	c.303-1052A>G		intron	N/A	ENSP00000387211.1	Q13478
	IL18R1	ENST00000410040.5	TSL:2	c.303-1052A>G		intron	N/A	ENSP00000386663.1	Q13478

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44308 AN: 152010 Hom.: 6836 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.291 AC: 44332 AN: 152126 Hom.: 6842 Cov.: 33 AF XY: 0.289 AC XY: 21474 AN XY: 74370

African (AFR) AF: 0.306 AC: 12698 AN: 41492

American (AMR) AF: 0.255 AC: 3908 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3466

East Asian (EAS) AF: 0.0715 AC: 371 AN: 5188

South Asian (SAS) AF: 0.189 AC: 912 AN: 4822

European-Finnish (FIN) AF: 0.327 AC: 3463 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20535 AN: 67960

Other (OTH) AF: 0.307 AC: 649 AN: 2114

Alfa AF: 0.290 Hom.: 4324

Bravo AF: 0.289

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		0.96
Mutation Taster		=100/0	polymorphism (auto)

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: rs7579737; hg19: chr2-102987361;