2-112781661-A-C

Position:

• chr2-112781661-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000575.5(IL1A):​c.262T>G​(p.Leu88Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IL1A NM_000575.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3116483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5	c.262T>G	p.Leu88Val	missense_variant	4/7	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1	c.262T>G	p.Leu88Val	missense_variant	4/7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4	c.262T>G	p.Leu88Val	missense_variant	4/7	1	NM_000575.5	ENSP00000263339	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.262T>G (p.L88V) alteration is located in exon 4 (coding exon 3) of the IL1A gene. This alteration results from a T to G substitution at nucleotide position 262, causing the leucine (L) at amino acid position 88 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.0091
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.023	D
Polyphen		0.94	P
Vest4		0.24
MutPred		0.60		Gain of catalytic residue at L88 (P = 0.0297);
MVP		0.76
MPC		0.78
ClinPred		0.57	D
GERP RS		3.4
Varity_R		0.12
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr2-113539238;