2-112775308-G-T

Variant summary

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

The NM_000575.5(IL1A):c.616-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,533,572 control chromosomes in the GnomAD database, including 364,237 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 (37275 hom., cov: 32)
  • Exomes 𝑓: 0.68 (326962 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815

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=-0.89).
• 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.616-41C>A		intron_variant		ENST00000263339.4
IL1A	NM_001371554.1	c.616-41C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1A	ENST00000263339.4	c.616-41C>A		intron_variant		1	NM_000575.5	P1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105291 AN: 152016 Hom.: 37236 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: 0.696

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.685

GnomAD3 exomes AF: 0.639 AC: 157385 AN: 246478 Hom.: 52697 AF XY: 0.650 AC XY: 86835 AN XY: 133544

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.295

Gnomad SAS exome AF: 0.721

Gnomad FIN exome AF: 0.606

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.682 AC: 942164 AN: 1381438 Hom.: 326962 Cov.: 21 AF XY: 0.685 AC XY: 473482 AN XY: 691376

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.735

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.612

Gnomad4 NFE exome AF: 0.701

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.693 AC: 105371 AN: 152134 Hom.: 37275 Cov.: 32 AF XY: 0.684 AC XY: 50872 AN XY: 74378

Gnomad4 AFR AF: 0.784

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.680

Alfa AF: 0.699 Hom.: 10023

Bravo AF: 0.691

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.45
Dann	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3783550; hg19: chr2-113532885; COSMIC: COSV54519146;