2-112784230-T-C

Position:

• chr2-112784230-T-C

Variant summary

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

The NM_000575.5(IL1A):​c.-9+213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,208 control chromosomes in the GnomAD database, including 42,148 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 0.73 (42148 hom., cov: 33)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.-9+213A>G		intron_variant		ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.-9+85A>G		intron_variant			NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.-9+213A>G		intron_variant		1	NM_000575.5	ENSP00000263339.3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 111093 AN: 152090 Hom.: 42102 Cov.: 33

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.720

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 111182 AN: 152208 Hom.: 42148 Cov.: 33 AF XY: 0.721 AC XY: 53643 AN XY: 74404

Gnomad4 AFR AF: 0.913

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.733

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.714

Alfa AF: 0.708 Hom.: 17121

Bravo AF: 0.733

Asia WGS AF: 0.533 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.48

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: rs3783526; hg19: chr2-113541807; COSMIC: COSV54518920;