chr2-102376215-T-C

Variant names:

• chr2-102376215-T-C
• rs2270297
• NM_003855.5:c.625+152T>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.625+152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 502,108 control chromosomes in the GnomAD database, including 145,114 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 0.77 (46375 hom., cov: 32)
  • Exomes 𝑓: 0.74 (98739 hom.)
• Consequence: IL18R1 NM_003855.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL18R1	NM_003855.5	c.625+152T>C		intron_variant	Intron 5 of 10	ENST00000233957.7	NP_003846.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL18R1	ENST00000233957.7	c.625+152T>C		intron_variant	Intron 5 of 10	5	NM_003855.5	ENSP00000233957.1
IL18R1	ENST00000409599.5	c.625+152T>C		intron_variant	Intron 6 of 11	5		ENSP00000387211.1
IL18R1	ENST00000410040.5	c.625+152T>C		intron_variant	Intron 5 of 10	2		ENSP00000386663.1
IL18R1	ENST00000677287.1	n.*169+152T>C		intron_variant	Intron 5 of 10			ENSP00000503023.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117405 AN: 152000 Hom.: 46331 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.756

GnomAD4 exome AF: 0.743 AC: 260206 AN: 349990 Hom.: 98739 AF XY: 0.739 AC XY: 132189 AN XY: 178916

African (AFR) AF: 0.892 AC: 7819 AN: 8768

American (AMR) AF: 0.529 AC: 4277 AN: 8082

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 7859 AN: 10254

East Asian (EAS) AF: 0.559 AC: 13385 AN: 23952

South Asian (SAS) AF: 0.527 AC: 6712 AN: 12744

European-Finnish (FIN) AF: 0.813 AC: 26615 AN: 32718

Middle Eastern (MID) AF: 0.736 AC: 1132 AN: 1538

European-Non Finnish (NFE) AF: 0.766 AC: 177686 AN: 232060

Other (OTH) AF: 0.741 AC: 14721 AN: 19874

GnomAD4 genome AF: 0.772 AC: 117499 AN: 152118 Hom.: 46375 Cov.: 32 AF XY: 0.766 AC XY: 56946 AN XY: 74330

African (AFR) AF: 0.889 AC: 36870 AN: 41496

American (AMR) AF: 0.602 AC: 9207 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2657 AN: 3468

East Asian (EAS) AF: 0.556 AC: 2871 AN: 5160

South Asian (SAS) AF: 0.546 AC: 2631 AN: 4820

European-Finnish (FIN) AF: 0.812 AC: 8573 AN: 10562

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52251 AN: 68008

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.740 Hom.: 9708

Bravo AF: 0.762

Asia WGS AF: 0.582 AC: 2025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.49
PhyloP100		0.071
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: rs2270297; hg19: chr2-102992675;