2-102387501-C-A

Variant names:

• chr2-102387501-C-A
• rs3771161
• NM_003855.5:c.949+501C>A

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+501C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,146 control chromosomes in the GnomAD database, including 3,829 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 0.21 (3829 hom., cov: 32)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.949+501C>A		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+501C>A		intron_variant	Intron 8 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.949+501C>A		intron_variant	Intron 9 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.949+501C>A		intron_variant	Intron 8 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*493+501C>A		intron_variant	Intron 8 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32293 AN: 152028 Hom.: 3826 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.212 AC: 32329 AN: 152146 Hom.: 3829 Cov.: 32 AF XY: 0.209 AC XY: 15545 AN XY: 74370

African (AFR) AF: 0.314 AC: 13025 AN: 41482

American (AMR) AF: 0.167 AC: 2557 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.0948 AC: 490 AN: 5170

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2014 AN: 10578

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12342 AN: 68008

Other (OTH) AF: 0.210 AC: 445 AN: 2116

Alfa AF: 0.194 Hom.: 789

Bravo AF: 0.215

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.16
DANN	Benign	0.56
PhyloP100		-1.1
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: rs3771161; hg19: chr2-103003961;