2-112775308-G-T

Variant names:

• chr2-112775308-G-T
• rs3783550
• NM_000575.5:c.616-41C>A

Variant summary

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

The NM_000575.5(IL1A):​c.616-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,533,572 control chromosomes in the GnomAD database, including 364,237 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 0.69 (37275 hom., cov: 32)
  • Exomes 𝑓: 0.68 (326962 hom.)
• Consequence: IL1A NM_000575.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.815
• Publications: 57 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.616-41C>A		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.616-41C>A		intron	N/A	NP_001358483.1	P01583

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	ENST00000263339.4	TSL:1 MANE Select	c.616-41C>A		intron	N/A	ENSP00000263339.3	P01583
	IL1A	ENST00000959423.1		c.616-41C>A		intron	N/A	ENSP00000629482.1
	ENSG00000299339	ENST00000762706.1		n.404+4412G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105291 AN: 152016 Hom.: 37236 Cov.: 32

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.774

Gnomad AMR AF: 0.604

Gnomad ASJ AF: 0.733

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.685

GnomAD2 exomes AF: 0.639 AC: 157385 AN: 246478 AF XY: 0.650

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.466

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.295

Gnomad FIN exome AF: 0.606

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.656

GnomAD4 exome AF: 0.682 AC: 942164 AN: 1381438 Hom.: 326962 Cov.: 21 AF XY: 0.685 AC XY: 473482 AN XY: 691376

African (AFR) AF: 0.793 AC: 25078 AN: 31620

American (AMR) AF: 0.481 AC: 21234 AN: 44162

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 18797 AN: 25574

East Asian (EAS) AF: 0.281 AC: 11044 AN: 39242

South Asian (SAS) AF: 0.721 AC: 60951 AN: 84510

European-Finnish (FIN) AF: 0.612 AC: 32621 AN: 53260

Middle Eastern (MID) AF: 0.748 AC: 4208 AN: 5624

European-Non Finnish (NFE) AF: 0.701 AC: 729348 AN: 1039844

Other (OTH) AF: 0.675 AC: 38883 AN: 57602

GnomAD4 genome AF: 0.693 AC: 105371 AN: 152134 Hom.: 37275 Cov.: 32 AF XY: 0.684 AC XY: 50872 AN XY: 74378

African (AFR) AF: 0.784 AC: 32546 AN: 41512

American (AMR) AF: 0.603 AC: 9216 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 2545 AN: 3470

East Asian (EAS) AF: 0.295 AC: 1529 AN: 5186

South Asian (SAS) AF: 0.696 AC: 3360 AN: 4828

European-Finnish (FIN) AF: 0.598 AC: 6318 AN: 10562

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47482 AN: 67976

Other (OTH) AF: 0.680 AC: 1437 AN: 2114

Alfa AF: 0.684 Hom.: 20019

Bravo AF: 0.691

Asia WGS AF: 0.521 AC: 1815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.41
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs3783550; hg19: chr2-113532885; COSMIC: COSV54519146;