rs2856841

chr2-112779762-A-Gchr2-112779762-A-T

Variant summary

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

The NM_000575.5(IL1A):c.320-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 764,626 control chromosomes in the GnomAD database, including 27,518 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 0.24 (5004 hom., cov: 32)
  • Exomes 𝑓: 0.26 (22514 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1A	NM_000575.5	c.320-96T>C		intron_variant		ENST00000263339.4
IL1A	NM_001371554.1	c.320-96T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1A	ENST00000263339.4	c.320-96T>C		intron_variant		1	NM_000575.5	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36785 AN: 152036 Hom.: 5004 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.264 AC: 161751 AN: 612472 Hom.: 22514 AF XY: 0.268 AC XY: 83092 AN XY: 310360

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.0927

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.274

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.242 AC: 36790 AN: 152154 Hom.: 5004 Cov.: 32 AF XY: 0.244 AC XY: 18168 AN XY: 74386

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0798

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.254

Alfa AF: 0.265 Hom.: 868

Bravo AF: 0.229

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.5
Dann	Benign	0.70

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: rs2856841; hg19: chr2-113537339; COSMIC: COSV54519650;