rs2856838

Variant names:

• chr2-112782395-G-A
• rs2856838
• NM_000575.5:c.96+321C>T

Variant summary

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

The ENST00000263339.4(IL1A):​c.96+321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,030 control chromosomes in the GnomAD database, including 10,455 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 0.37 (10455 hom., cov: 32)
• Consequence: IL1A ENST00000263339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 29 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263339.4. 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+321C>T		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.96+321C>T		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+321C>T		intron	N/A	ENSP00000263339.3
	ENSG00000299339	ENST00000762706.1		n.404+11499G>A		intron	N/A
	ENSG00000299339	ENST00000762707.1		n.499+11499G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55854 AN: 151910 Hom.: 10452 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.367 AC: 55868 AN: 152030 Hom.: 10455 Cov.: 32 AF XY: 0.359 AC XY: 26694 AN XY: 74302

African (AFR) AF: 0.366 AC: 15196 AN: 41466

American (AMR) AF: 0.308 AC: 4705 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3470

East Asian (EAS) AF: 0.215 AC: 1109 AN: 5162

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4816

European-Finnish (FIN) AF: 0.281 AC: 2969 AN: 10550

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27396 AN: 67968

Other (OTH) AF: 0.368 AC: 778 AN: 2112

Alfa AF: 0.391 Hom.: 4525

Bravo AF: 0.366

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		-0.29
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: rs2856838; hg19: chr2-113539972;