chr2-112782600-C-T

Position:

• chr2-112782600-C-T

Variant summary

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

The NM_000575.5(IL1A):​c.96+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 727,972 control chromosomes in the GnomAD database, including 32,878 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 (7964 hom., cov: 33)
  • Exomes 𝑓: 0.29 (24914 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.96+116G>A		intron_variant		ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.96+116G>A		intron_variant			NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.96+116G>A		intron_variant		1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48232 AN: 151978 Hom.: 7951 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.289 AC: 166467 AN: 575876 Hom.: 24914 AF XY: 0.290 AC XY: 88880 AN XY: 306510

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.0907

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.317 AC: 48287 AN: 152096 Hom.: 7964 Cov.: 33 AF XY: 0.317 AC XY: 23595 AN XY: 74354

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0792

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.308

Alfa AF: 0.316 Hom.: 1180

Bravo AF: 0.316

Asia WGS AF: 0.214 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.2
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1894399; hg19: chr2-113540177;