rs2856836

Variant names:

• chr2-112774506-A-G
• rs2856836
• NM_000575.5:c.*561T>C

Variant summary

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

The NM_000575.5(IL1A):​c.*561T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.256 in 151,728 control chromosomes in the GnomAD database, including 5,310 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 (5310 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: IL1A NM_000575.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.91

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 (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_000575.5	ENSP00000263339.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38870 AN: 151618 Hom.: 5306 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.264

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.256 AC: 38894 AN: 151728 Hom.: 5310 Cov.: 32 AF XY: 0.259 AC XY: 19171 AN XY: 74144

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.263

Alfa AF: 0.271 Hom.: 2235

Bravo AF: 0.246

Asia WGS AF: 0.201 AC: 699 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	15
DANN	Benign	0.73

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: rs2856836; hg19: chr2-113532083;