NM_000575.5:c.320-96T>C

Variant names:

• chr2-112779762-A-G
• rs2856841
• NM_000575.5:c.320-96T>C

Variant summary

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

The NM_000575.5(IL1A):​c.320-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 764,626 control chromosomes in the GnomAD database, including 27,518 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 0.24 (5004 hom., cov: 32)
  • Exomes 𝑓: 0.26 (22514 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 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.320-96T>C		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.320-96T>C		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.320-96T>C		intron	N/A	ENSP00000263339.3
	ENSG00000299339	ENST00000762706.1		n.404+8866A>G		intron	N/A
	ENSG00000299339	ENST00000762707.1		n.499+8866A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36785 AN: 152036 Hom.: 5004 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0798

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.264 AC: 161751 AN: 612472 Hom.: 22514 AF XY: 0.268 AC XY: 83092 AN XY: 310360

African (AFR) AF: 0.118 AC: 1860 AN: 15802

American (AMR) AF: 0.236 AC: 5043 AN: 21398

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 4470 AN: 13286

East Asian (EAS) AF: 0.0927 AC: 2829 AN: 30524

South Asian (SAS) AF: 0.297 AC: 7551 AN: 25408

European-Finnish (FIN) AF: 0.313 AC: 10945 AN: 34954

Middle Eastern (MID) AF: 0.330 AC: 692 AN: 2100

European-Non Finnish (NFE) AF: 0.274 AC: 120662 AN: 439880

Other (OTH) AF: 0.264 AC: 7699 AN: 29120

GnomAD4 genome AF: 0.242 AC: 36790 AN: 152154 Hom.: 5004 Cov.: 32 AF XY: 0.244 AC XY: 18168 AN XY: 74386

African (AFR) AF: 0.128 AC: 5304 AN: 41508

American (AMR) AF: 0.264 AC: 4045 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3468

East Asian (EAS) AF: 0.0798 AC: 413 AN: 5178

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3344 AN: 10584

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20047 AN: 67980

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.261 Hom.: 881

Bravo AF: 0.229

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2856841; hg19: chr2-113537339; COSMIC: COSV54519650;