2-102168373-A-G

Variant names:

• chr2-102168373-A-G
• rs3917296
• NM_000877.4:c.656-225A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	NM_000877.4	MANE Select	c.656-225A>G		intron	N/A	NP_000868.1
	IL1R1	NM_001320978.2		c.656-225A>G		intron	N/A	NP_001307907.1
	IL1R1	NM_001320980.2		c.656-225A>G		intron	N/A	NP_001307909.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1R1	ENST00000410023.6	TSL:1 MANE Select	c.656-225A>G		intron	N/A	ENSP00000386380.1
	IL1R1	ENST00000409929.5	TSL:1	c.656-225A>G		intron	N/A	ENSP00000386776.1
	IL1R1	ENST00000409288.5	TSL:5	c.656-225A>G		intron	N/A	ENSP00000386478.1

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

African (AFR) AF: 0.0183 AC: 759 AN: 41536

American (AMR) AF: 0.0900 AC: 1375 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3468

East Asian (EAS) AF: 0.179 AC: 926 AN: 5180

South Asian (SAS) AF: 0.118 AC: 567 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1133 AN: 10604

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0786 AC: 5340 AN: 67966

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0734 Hom.: 303

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

Feb 01, 2021

Beijing Anzhen Hospital, Capital Medical University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0080
DANN	Benign	0.30
PhyloP100		-3.4
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: rs3917296; hg19: chr2-102784833;