rs12998521

Positions:

• chr2-102357957-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003855.5(IL18R1):​c.-29+1557G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,682 control chromosomes in the GnomAD database, including 8,376 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 0.32 (8376 hom., cov: 31)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.999

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.-29+1557G>T		intron_variant		ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.-29+1557G>T		intron_variant		5	NM_003855.5	ENSP00000233957	P1
IL18R1	ENST00000409599.5	c.-29+1557G>T		intron_variant		5		ENSP00000387211	P1
IL18R1	ENST00000410040.5	c.-28-4676G>T		intron_variant		2		ENSP00000386663
IL18R1	ENST00000466357.1	n.356+1557G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.317 AC: 47980 AN: 151564 Hom.: 8375 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.316 AC: 48003 AN: 151682 Hom.: 8376 Cov.: 31 AF XY: 0.317 AC XY: 23502 AN XY: 74088

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.351

Alfa AF: 0.351 Hom.: 3363

Bravo AF: 0.299

Asia WGS AF: 0.408 AC: 1419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.41

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: rs12998521; hg19: chr2-102974417;