2-112779527-C-T

Variant names:

• chr2-112779527-C-T
• rs138168355
• NM_000575.5:c.459G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_000575.5(IL1A):​c.459G>A​(p.Thr153Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,601,802 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: IL1A NM_000575.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.38
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 2-112779527-C-T is Benign according to our data. Variant chr2-112779527-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 740365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.38 with no splicing effect.

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.459G>A	p.Thr153Thr	synonymous	Exon 5 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.459G>A	p.Thr153Thr	synonymous	Exon 5 of 7	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.459G>A	p.Thr153Thr	synonymous	Exon 5 of 7	ENSP00000263339.3	P01583
	IL1A	ENST00000959423.1		c.459G>A	p.Thr153Thr	synonymous	Exon 4 of 6	ENSP00000629482.1
	ENSG00000299339	ENST00000762706.1		n.404+8631C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000507 AC: 127 AN: 250492 AF XY: 0.000657

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000450

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000364 AC: 528 AN: 1449578 Hom.: 1 Cov.: 30 AF XY: 0.000408 AC XY: 294 AN XY: 720336

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.0000225 AC: 1 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.00233 AC: 60 AN: 25732

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.00145 AC: 124 AN: 85292

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53072

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5708

European-Non Finnish (NFE) AF: 0.000261 AC: 288 AN: 1102824

Other (OTH) AF: 0.000636 AC: 38 AN: 59724

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74398

African (AFR) AF: 0.0000481 AC: 2 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000605 Hom.: 0

Bravo AF: 0.000257

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs138168355; hg19: chr2-113537104;