chr2-112784348-G-A

Position:

• chr2-112784348-G-A

Variant summary

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

The ENST00000263339.4(IL1A):​c.-9+95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,430 control chromosomes in the GnomAD database, including 5,568 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 0.26 (5564 hom., cov: 33)
  • Exomes 𝑓: 0.22 (4 hom.)
• Consequence: IL1A ENST00000263339.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.-9+95C>T		intron_variant		ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.-42C>T		5_prime_UTR_variant	1/7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.-9+95C>T		intron_variant		1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40289 AN: 152080 Hom.: 5561 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0793

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.220 AC: 51 AN: 232 Hom.: 4 AF XY: 0.239 AC XY: 32 AN XY: 134

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.265 AC: 40315 AN: 152198 Hom.: 5564 Cov.: 33 AF XY: 0.267 AC XY: 19869 AN XY: 74408

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.0793

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.270

Alfa AF: 0.289 Hom.: 10679

Bravo AF: 0.255

Asia WGS AF: 0.204 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.0
DANN	Benign	0.45

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: rs2856837; hg19: chr2-113541925;