chr2-112782628-G-T

Variant names:

• chr2-112782628-G-T
• rs1609682
• NM_000575.5:c.96+88C>A

Variant summary

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

The NM_000575.5(IL1A):​c.96+88C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 961,772 control chromosomes in the GnomAD database, including 225,056 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 (37278 hom., cov: 33)
  • Exomes 𝑓: 0.67 (187778 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• 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=-0.9).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.96+88C>A		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.96+88C>A		intron	N/A	NP_001358483.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.96+88C>A		intron	N/A	ENSP00000263339.3
	IL1A	ENST00000959423.1		c.96+88C>A		intron	N/A	ENSP00000629482.1
	ENSG00000299339	ENST00000762706.1		n.404+11732G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105294 AN: 152004 Hom.: 37239 Cov.: 33

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.295

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

GnomAD4 exome AF: 0.672 AC: 543946 AN: 809650 Hom.: 187778 AF XY: 0.676 AC XY: 286573 AN XY: 423716

African (AFR) AF: 0.792 AC: 15911 AN: 20102

American (AMR) AF: 0.479 AC: 17953 AN: 37504

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 14751 AN: 20124

East Asian (EAS) AF: 0.281 AC: 10163 AN: 36198

South Asian (SAS) AF: 0.722 AC: 48553 AN: 67282

European-Finnish (FIN) AF: 0.613 AC: 31345 AN: 51170

Middle Eastern (MID) AF: 0.744 AC: 3268 AN: 4392

European-Non Finnish (NFE) AF: 0.704 AC: 375971 AN: 534218

Other (OTH) AF: 0.673 AC: 26031 AN: 38660

GnomAD4 genome AF: 0.693 AC: 105374 AN: 152122 Hom.: 37278 Cov.: 33 AF XY: 0.684 AC XY: 50867 AN XY: 74362

African (AFR) AF: 0.784 AC: 32532 AN: 41496

American (AMR) AF: 0.603 AC: 9218 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2543 AN: 3470

East Asian (EAS) AF: 0.294 AC: 1524 AN: 5178

South Asian (SAS) AF: 0.696 AC: 3360 AN: 4828

European-Finnish (FIN) AF: 0.598 AC: 6314 AN: 10550

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

European-Non Finnish (NFE) AF: 0.699 AC: 47506 AN: 67992

Other (OTH) AF: 0.680 AC: 1439 AN: 2116

Alfa AF: 0.706 Hom.: 5782

Bravo AF: 0.691

Asia WGS AF: 0.523 AC: 1821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.078
DANN	Benign	0.65
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1609682; hg19: chr2-113540205; COSMIC: COSV54519157;