rs1304037

Positions:

• chr2-112774659-T-C

Variant summary

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

The ENST00000263339.4(IL1A):​c.*408A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 157,704 control chromosomes in the GnomAD database, including 8,122 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 0.32 (7899 hom., cov: 31)
  • Exomes 𝑓: 0.26 (223 hom.)
• Consequence: IL1A ENST00000263339.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.*408A>G		3_prime_UTR_variant	7/7	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.*408A>G		3_prime_UTR_variant	7/7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.*408A>G		3_prime_UTR_variant	7/7	1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47933 AN: 151676 Hom.: 7876 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.257 AC: 1519 AN: 5914 Hom.: 223 Cov.: 0 AF XY: 0.256 AC XY: 804 AN XY: 3142

Gnomad4 AFR exome AF: 0.344

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0663

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.309

GnomAD4 genome AF: 0.316 AC: 47999 AN: 151790 Hom.: 7899 Cov.: 31 AF XY: 0.316 AC XY: 23422 AN XY: 74168

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.306

Alfa AF: 0.311 Hom.: 2204

Bravo AF: 0.315

Asia WGS AF: 0.214 AC: 747 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.85

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: rs1304037; hg19: chr2-113532236;