2-102168373-A-G

Variant summary

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

The NM_000877.4(IL1R1):c.656-225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 152,174 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.072 (503 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -3.42

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.656-225A>G		intron_variant		ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.656-225A>G		intron_variant		1	NM_000877.4	P1

Frequencies

GnomAD3 genomes AF: 0.0720 AC: 10942 AN: 152056 Hom.: 499 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0902

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0865

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

GnomAD4 genome AF: 0.0720 AC: 10952 AN: 152174 Hom.: 503 Cov.: 32 AF XY: 0.0750 AC XY: 5580 AN XY: 74398

Gnomad4 AFR AF: 0.0183

Gnomad4 AMR AF: 0.0900

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0725 Hom.: 283

Bravo AF: 0.0700

Asia WGS AF: 0.155 AC: 540 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.0080
Dann	Benign	0.30

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: rs3917296; hg19: chr2-102784833;