2-112779646-C-G

Variant names:

• chr2-112779646-C-G
• NM_000575.5:c.340G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000575.5(IL1A):​c.340G>C​(p.Ala114Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A114S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1A NM_000575.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5	c.340G>C	p.Ala114Pro	missense_variant	Exon 5 of 7	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.340G>C	p.Ala114Pro	missense_variant	Exon 5 of 7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.340G>C	p.Ala114Pro	missense_variant	Exon 5 of 7	1	NM_000575.5	ENSP00000263339.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.042
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.11
Sift	Benign	0.12	T
Sift4G	Uncertain	0.029	D
Polyphen		0.99	D
Vest4		0.35
MutPred		0.53		Gain of glycosylation at A114 (P = 0.0073);
MVP		0.73
MPC		0.93
ClinPred		0.51	D
GERP RS		4.4
Varity_R		0.33
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-113537223;