2-102159742-C-T

Variant summary

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

The NM_000877.4(IL1R1):c.61+1957C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,138 control chromosomes in the GnomAD database, including 2,116 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.14 (2116 hom., cov: 32)
• Consequence: IL1R1 NM_000877.4 intron
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.305

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1R1	NM_000877.4	c.61+1957C>T		intron_variant		ENST00000410023.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1R1	ENST00000410023.6	c.61+1957C>T		intron_variant		1	NM_000877.4	P1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21349 AN: 152020 Hom.: 2111 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.0678

Gnomad FIN AF: 0.0539

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.141 AC: 21386 AN: 152138 Hom.: 2116 Cov.: 32 AF XY: 0.141 AC XY: 10463 AN XY: 74386

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.0539

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0981 Hom.: 891

Bravo AF: 0.155

Asia WGS AF: 0.124 AC: 429 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	-0.90
Cadd	Benign	3.2
Dann	Benign	0.37

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: rs13019803; hg19: chr2-102776202;