rs3917254

Variant names:

• chr2-102160058-G-A
• rs3917254
• NM_000877.4:c.61+2273G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IL1R1	NM_000877.4	c.61+2273G>A		intron_variant	Intron 3 of 11	ENST00000410023.6	NP_000868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1R1	ENST00000410023.6	c.61+2273G>A		intron_variant	Intron 3 of 11	1	NM_000877.4	ENSP00000386380.1

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

African (AFR) AF: 0.301 AC: 12465 AN: 41430

American (AMR) AF: 0.174 AC: 2661 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0924 AC: 320 AN: 3464

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5162

South Asian (SAS) AF: 0.190 AC: 916 AN: 4820

European-Finnish (FIN) AF: 0.0553 AC: 583 AN: 10552

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0923 AC: 6270 AN: 67960

Other (OTH) AF: 0.147 AC: 311 AN: 2114

Alfa AF: 0.119 Hom.: 2866

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

Feb 01, 2021

Beijing Anzhen Hospital, Capital Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3917254; hg19: chr2-102776518;