2-102357669-C-T

Variant names:

• chr2-102357669-C-T
• rs12999364
• NM_003855.5:c.-29+1269C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003855.5(IL18R1):​c.-29+1269C>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 151,770 control chromosomes in the GnomAD database, including 8,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (★★).

• Frequency: Genomes: 𝑓 0.32 (8367 hom., cov: 30)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Benign; association criteria provided, multiple submitters, no conflicts B:1 O:1
• Conservation: PhyloP100: -1.25
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-102357669-C-T is Benign according to our data. Variant chr2-102357669-C-T is described in ClinVar as Benign|association. ClinVar VariationId is 916546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.-29+1269C>T		intron_variant	Intron 1 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.-29+1269C>T		intron_variant	Intron 1 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.-29+1269C>T		intron_variant	Intron 2 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.-28-4964C>T		intron_variant	Intron 1 of 10	2		ENSP00000386663.1
IL18R1	ENST00000466357.1	n.356+1269C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47973 AN: 151652 Hom.: 8366 Cov.: 30

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.316 AC: 47996 AN: 151770 Hom.: 8367 Cov.: 30 AF XY: 0.317 AC XY: 23503 AN XY: 74154

African (AFR) AF: 0.170 AC: 7029 AN: 41364

American (AMR) AF: 0.278 AC: 4235 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2194 AN: 5134

South Asian (SAS) AF: 0.357 AC: 1711 AN: 4798

European-Finnish (FIN) AF: 0.389 AC: 4083 AN: 10504

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26534 AN: 67928

Other (OTH) AF: 0.353 AC: 744 AN: 2108

Alfa AF: 0.279 Hom.: 2129

Bravo AF: 0.299

Asia WGS AF: 0.408 AC: 1418 AN: 3478

ClinVar

Significance: Benign; association

Submissions summary: Benign:1 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Jul 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28121058) -

Behcet disease Other:1

Jan 29, 2020

Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University

Significance: association

Review Status: criteria provided, single submitter

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-1.2
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: rs12999364; hg19: chr2-102974129;