Variant 2-112779624-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000575.5(IL1A):c.362A>G(p.Asn121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,612,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

IL1A
NM_000575.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.472

Variant links:

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]

IL1A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087007284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IL1A	NM_000575.5 linkuse as main transcript	c.362A>G	p.Asn121Ser	missense_variant	5/7	ENST00000263339.4	NP_000566.3	P01583
IL1A	NM_001371554.1 linkuse as main transcript	c.362A>G	p.Asn121Ser	missense_variant	5/7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 linkuse as main transcript	c.362A>G	p.Asn121Ser	missense_variant	5/7	1	NM_000575.5	ENSP00000263339.3		P01583

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459912

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725988

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.362A>G (p.N121S) alteration is located in exon 5 (coding exon 4) of the IL1A gene. This alteration results from a A to G substitution at nucleotide position 362, causing the asparagine (N) at amino acid position 121 to be replaced by a serine (S). 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

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.3

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.62

M_CAP

Benign

0.0018

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

REVEL

Benign

0.044

Sift

Benign

0.041

Sift4G

Benign

0.076

Polyphen

0.027

Vest4

0.077

MutPred

0.46

Gain of sheet (P = 0.0266);

MVP

0.42

MPC

0.52

ClinPred

0.090

GERP RS

-0.63

Varity_R

0.18

gMVP

0.098

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over