Genetic Variant NM_000575.5:c.340G>A (chr2-112779646-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is . The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000575.5(IL1A):c.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IL1A
NM_000575.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.83

Publications

0 publications found

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:

ENSG00000299339 (HGNC:):

ENSG00000299339 links:

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new If you want to explore the variant's impact on the transcript NM_000575.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (REVEL=0.082).

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.340G>A	p.Ala114Thr	missense	Exon 5 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.340G>A	p.Ala114Thr	missense	Exon 5 of 7	NP_001358483.1	P01583

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IL1A	ENST00000263339.4	TSL:1 MANE Select	c.340G>A	p.Ala114Thr	missense	Exon 5 of 7	ENSP00000263339.3	P01583
IL1A	ENST00000959423.1		c.340G>A	p.Ala114Thr	missense	Exon 4 of 6	ENSP00000629482.1
ENSG00000299339	ENST00000762706.1		n.404+8750C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453624

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39452

South Asian (SAS)

AF:

0.00

AC:

AN:

85918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1105308

Other (OTH)

AF:

0.00

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.77

M_CAP

Benign

0.0032

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

2.8

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.86

REVEL

Benign

0.082

Sift

Benign

0.19

Sift4G

Uncertain

0.053

Varity_R

0.077

gMVP

0.15

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over