chr2-112774659-T-C

Variant names:

• chr2-112774659-T-C
• rs1304037
• NM_000575.5:c.*408A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000575.5(IL1A):​c.*408A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 157,704 control chromosomes in the GnomAD database, including 8,122 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 (7899 hom., cov: 31)
  • Exomes 𝑓: 0.26 (223 hom.)
• Consequence: IL1A NM_000575.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 25 publications found

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]

ENSG00000299339 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000575.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.*408A>G		3_prime_UTR	Exon 7 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.*408A>G		3_prime_UTR	Exon 7 of 7	NP_001358483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.*408A>G		3_prime_UTR	Exon 7 of 7	ENSP00000263339.3
	ENSG00000299339	ENST00000762706.1		n.404+3763T>C		intron	N/A
	ENSG00000299339	ENST00000762707.1		n.499+3763T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47933 AN: 151676 Hom.: 7876 Cov.: 31

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.0790

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.257 AC: 1519 AN: 5914 Hom.: 223 Cov.: 0 AF XY: 0.256 AC XY: 804 AN XY: 3142

African (AFR) AF: 0.344 AC: 31 AN: 90

American (AMR) AF: 0.239 AC: 287 AN: 1202

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 25 AN: 88

East Asian (EAS) AF: 0.0663 AC: 24 AN: 362

South Asian (SAS) AF: 0.293 AC: 167 AN: 570

European-Finnish (FIN) AF: 0.224 AC: 17 AN: 76

Middle Eastern (MID) AF: 0.250 AC: 2 AN: 8

European-Non Finnish (NFE) AF: 0.272 AC: 898 AN: 3298

Other (OTH) AF: 0.309 AC: 68 AN: 220

GnomAD4 genome AF: 0.316 AC: 47999 AN: 151790 Hom.: 7899 Cov.: 31 AF XY: 0.316 AC XY: 23422 AN XY: 74168

African (AFR) AF: 0.387 AC: 16017 AN: 41356

American (AMR) AF: 0.291 AC: 4441 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1191 AN: 3466

East Asian (EAS) AF: 0.0790 AC: 408 AN: 5164

South Asian (SAS) AF: 0.301 AC: 1448 AN: 4816

European-Finnish (FIN) AF: 0.314 AC: 3294 AN: 10498

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20074 AN: 67920

Other (OTH) AF: 0.306 AC: 645 AN: 2110

Alfa AF: 0.311 Hom.: 2251

Bravo AF: 0.315

Asia WGS AF: 0.214 AC: 747 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1304037; hg19: chr2-113532236;