chr2-102389927-A-G

Variant names:

• chr2-102389927-A-G
• rs4851570
• NM_003855.5:c.950-129A>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.950-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 699,800 control chromosomes in the GnomAD database, including 25,975 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 0.24 (4757 hom., cov: 33)
  • Exomes 𝑓: 0.27 (21218 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768
• Publications: 13 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 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.950-129A>G		intron	N/A	NP_003846.1	Q13478
	IL18R1	NM_001371418.1		c.950-132A>G		intron	N/A	NP_001358347.1	B7ZKV7
	IL18R1	NM_001371419.1		c.950-129A>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.950-129A>G		intron	N/A	ENSP00000233957.1	Q13478
	IL18R1	ENST00000409599.5	TSL:5	c.950-129A>G		intron	N/A	ENSP00000387211.1	Q13478
	IL18R1	ENST00000410040.5	TSL:2	c.950-129A>G		intron	N/A	ENSP00000386663.1	Q13478

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36117 AN: 152066 Hom.: 4759 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.273 AC: 149427 AN: 547614 Hom.: 21218 AF XY: 0.274 AC XY: 78565 AN XY: 286532

African (AFR) AF: 0.149 AC: 2168 AN: 14550

American (AMR) AF: 0.181 AC: 4249 AN: 23532

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 2390 AN: 15204

East Asian (EAS) AF: 0.386 AC: 12261 AN: 31796

South Asian (SAS) AF: 0.286 AC: 14225 AN: 49762

European-Finnish (FIN) AF: 0.280 AC: 9510 AN: 33970

Middle Eastern (MID) AF: 0.172 AC: 647 AN: 3768

European-Non Finnish (NFE) AF: 0.279 AC: 96378 AN: 345434

Other (OTH) AF: 0.257 AC: 7599 AN: 29598

GnomAD4 genome AF: 0.237 AC: 36126 AN: 152186 Hom.: 4757 Cov.: 33 AF XY: 0.237 AC XY: 17643 AN XY: 74392

African (AFR) AF: 0.156 AC: 6479 AN: 41530

American (AMR) AF: 0.189 AC: 2892 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.405 AC: 2095 AN: 5174

South Asian (SAS) AF: 0.280 AC: 1353 AN: 4826

European-Finnish (FIN) AF: 0.269 AC: 2848 AN: 10580

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19181 AN: 67992

Other (OTH) AF: 0.237 AC: 500 AN: 2110

Alfa AF: 0.214 Hom.: 863

Bravo AF: 0.227

Asia WGS AF: 0.350 AC: 1216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.77
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: rs4851570; hg19: chr2-103006387; COSMIC: COSV52124250;