rs2071375

Positions:

• chr2-112777861-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.615+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 881,608 control chromosomes in the GnomAD database, including 35,891 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 0.26 (5337 hom., cov: 32)
  • Exomes 𝑓: 0.28 (30554 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IL1A	NM_000575.5	c.615+126G>A		intron_variant		ENST00000263339.4
IL1A	NM_001371554.1	c.615+126G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IL1A	ENST00000263339.4	c.615+126G>A		intron_variant		1	NM_000575.5	P1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39036 AN: 151946 Hom.: 5333 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0795

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.283 AC: 206712 AN: 729544 Hom.: 30554 AF XY: 0.285 AC XY: 107766 AN XY: 378034

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.0911

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.295

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.257 AC: 39062 AN: 152064 Hom.: 5337 Cov.: 32 AF XY: 0.259 AC XY: 19266 AN XY: 74328

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0795

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.263

Alfa AF: 0.274 Hom.: 902

Bravo AF: 0.246

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.49
DANN	Benign	0.89

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: rs2071375; hg19: chr2-113535438;