chr2-102388498-T-C

Variant names:

• chr2-102388498-T-C
• rs3771159
• NM_003855.5:c.949+1498T>C

Variant summary

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

The NM_003855.5(IL18R1):​c.949+1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,990 control chromosomes in the GnomAD database, including 23,602 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 0.53 (23602 hom., cov: 31)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.949+1498T>C		intron_variant	Intron 8 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.949+1498T>C		intron_variant	Intron 8 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.949+1498T>C		intron_variant	Intron 9 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.949+1498T>C		intron_variant	Intron 8 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*493+1498T>C		intron_variant	Intron 8 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81222 AN: 151872 Hom.: 23571 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.535 AC: 81306 AN: 151990 Hom.: 23602 Cov.: 31 AF XY: 0.529 AC XY: 39279 AN XY: 74262

African (AFR) AF: 0.732 AC: 30352 AN: 41456

American (AMR) AF: 0.413 AC: 6308 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2128 AN: 3466

East Asian (EAS) AF: 0.151 AC: 778 AN: 5154

South Asian (SAS) AF: 0.266 AC: 1280 AN: 4820

European-Finnish (FIN) AF: 0.543 AC: 5739 AN: 10566

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.486 AC: 33033 AN: 67944

Other (OTH) AF: 0.521 AC: 1102 AN: 2114

Alfa AF: 0.490 Hom.: 5472

Bravo AF: 0.535

Asia WGS AF: 0.232 AC: 809 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	2.1
DANN	Benign	0.42
PhyloP100		-0.16
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: rs3771159; hg19: chr2-103004958;