2-112775762-A-G

Position:

• chr2-112775762-A-G

Variant summary

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

The NM_000575.5(IL1A):​c.616-495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 152,044 control chromosomes in the GnomAD database, including 11,277 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 0.38 (11277 hom., cov: 31)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.430

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.616-495T>C		intron_variant		ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.616-495T>C		intron_variant			NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.616-495T>C		intron_variant		1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57992 AN: 151928 Hom.: 11273 Cov.: 31

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.382 AC: 58011 AN: 152044 Hom.: 11277 Cov.: 31 AF XY: 0.373 AC XY: 27717 AN XY: 74324

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.313

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.380

Alfa AF: 0.394 Hom.: 1725

Bravo AF: 0.383

Asia WGS AF: 0.310 AC: 1080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3783547; hg19: chr2-113533339;