2-102160058-G-A

Variant summary

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

The NM_000877.4(IL1R1):c.61+2273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 151,980 control chromosomes in the GnomAD database, including 2,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.16 (2696 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.365

Genes affected

IL1R1 (HGNC:5993): (interleukin 1 receptor type 1) This gene encodes a cytokine receptor that belongs to the interleukin-1 receptor family. The encoded protein is a receptor for interleukin-1 alpha, interleukin-1 beta, and interleukin-1 receptor antagonist. It is an important mediator involved in many cytokine-induced immune and inflammatory responses. This gene is located in a cluster of related cytokine receptor genes on chromosome 2q12. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.61+2273G>A		intron_variant		ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.61+2273G>A		intron_variant		1	NM_000877.4	P1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24867 AN: 151862 Hom.: 2691 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0924

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0553

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.164 AC: 24895 AN: 151980 Hom.: 2696 Cov.: 32 AF XY: 0.165 AC XY: 12277 AN XY: 74266

Gnomad4 AFR AF: 0.301

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0924

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0553

Gnomad4 NFE AF: 0.0923

Gnomad4 OTH AF: 0.147

Alfa AF: 0.113 Hom.: 1664

Bravo AF: 0.178

Asia WGS AF: 0.194 AC: 675 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Ascending aortic dissection Other:1

association, no assertion criteria provided

case-control

Beijing Anzhen Hospital, Capital Medical University

Feb 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.7
Dann	Benign	0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3917254; hg19: chr2-102776518;