rs3783543

chr2-112779074-A-G

Variant summary

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

The NM_000575.5(IL1A):c.490+422T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,102 control chromosomes in the GnomAD database, including 37,283 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (37283 hom., cov: 32)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

Genes affected

IL1A (HGNC:5991): (interleukin 1 alpha) The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1A	NM_000575.5	c.490+422T>C		intron_variant		ENST00000263339.4
IL1A	NM_001371554.1	c.490+422T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1A	ENST00000263339.4	c.490+422T>C		intron_variant		1	NM_000575.5	P1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105294 AN: 151984 Hom.: 37244 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.693 AC: 105374 AN: 152102 Hom.: 37283 Cov.: 32 AF XY: 0.684 AC XY: 50861 AN XY: 74330

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.680

Alfa AF: 0.710 Hom.: 5490

Bravo AF: 0.691

Asia WGS AF: 0.522 AC: 1816 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	8.0
Dann	Benign	0.86

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: rs3783543; hg19: chr2-113536651;