2-112777253-G-C

Variant names:

• chr2-112777253-G-C
• rs3783546
• NM_000575.5:c.615+734C>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.615+734C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,060 control chromosomes in the GnomAD database, including 37,264 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 0.69 (37264 hom., cov: 32)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 31 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.615+734C>G		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.615+734C>G		intron	N/A	NP_001358483.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.615+734C>G		intron	N/A	ENSP00000263339.3
	IL1A	ENST00000959423.1		c.615+734C>G		intron	N/A	ENSP00000629482.1
	ENSG00000299339	ENST00000762706.1		n.404+6357G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105250 AN: 151942 Hom.: 37225 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.693 AC: 105330 AN: 152060 Hom.: 37264 Cov.: 32 AF XY: 0.684 AC XY: 50832 AN XY: 74322

African (AFR) AF: 0.784 AC: 32528 AN: 41486

American (AMR) AF: 0.603 AC: 9217 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2545 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1516 AN: 5162

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4824

European-Finnish (FIN) AF: 0.598 AC: 6312 AN: 10558

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47480 AN: 67966

Other (OTH) AF: 0.680 AC: 1435 AN: 2110

Alfa AF: 0.593 Hom.: 1640

Bravo AF: 0.691

Asia WGS AF: 0.522 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.5
DANN	Benign	0.65
PhyloP100		2.2
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: rs3783546; hg19: chr2-113534830;