chr2-112782395-G-A

Position:

• chr2-112782395-G-A

Variant summary

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

The NM_000575.5(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 NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.96+321C>T		intron_variant		ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.96+321C>T		intron_variant			NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.96+321C>T		intron_variant		1	NM_000575.5	ENSP00000263339	P1

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

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.368

Alfa AF: 0.389 Hom.: 2767

Bravo AF: 0.366

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs2856838; hg19: chr2-113539972;