Genetic Variant IL1A:c.96+116G>A (chr2-112782600-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000575.5(IL1A):c.96+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 727,972 control chromosomes in the GnomAD database, including 32,878 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 7964 hom., cov: 33)

Exomes 𝑓: 0.29 ( 24914 hom. )

Consequence

IL1A
NM_000575.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340

Publications

13 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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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5 link	c.96+116G>A		intron_variant	Intron 3 of 6	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1 link	c.96+116G>A		intron_variant	Intron 3 of 6		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 link	c.96+116G>A		intron_variant	Intron 3 of 6	1	NM_000575.5	ENSP00000263339.3

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48232

AN:

151978

Hom.:

7951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.292

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0792

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.310

GnomAD4 exome

AF:

0.289

AC:

166467

AN:

575876

Hom.:

24914

AF XY:

0.290

AC XY:

88880

AN XY:

306510

show subpopulations

African (AFR)

AF:

0.384

AC:

5834

AN:

15178

American (AMR)

AF:

0.244

AC:

7353

AN:

30192

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

5484

AN:

16176

East Asian (EAS)

AF:

0.0907

AC:

3123

AN:

34434

South Asian (SAS)

AF:

0.307

AC:

16679

AN:

54412

European-Finnish (FIN)

AF:

0.313

AC:

14376

AN:

45926

Middle Eastern (MID)

AF:

0.378

AC:

1454

AN:

3844

European-Non Finnish (NFE)

AF:

0.299

AC:

103040

AN:

345166

Other (OTH)

AF:

0.299

AC:

9124

AN:

30548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

5532

11065

16597

22130

27662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1060

2120

3180

4240

5300

<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

AF:

0.317

AC:

48287

AN:

152096

Hom.:

7964

Cov.:

AF XY:

0.317

AC XY:

23595

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.391

AC:

16224

AN:

41494

American (AMR)

AF:

0.292

AC:

4457

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3472

East Asian (EAS)

AF:

0.0792

AC:

410

AN:

5176

South Asian (SAS)

AF:

0.299

AC:

1441

AN:

4816

European-Finnish (FIN)

AF:

0.316

AC:

3342

AN:

10562

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.295

AC:

20089

AN:

67984

Other (OTH)

AF:

0.308

AC:

650

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1683

3365

5048

6730

8413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.317

Hom.:

1232

Bravo

AF:

0.316

Asia WGS

AF:

0.214

AC:

747

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.2

(source)

DANN

Benign

0.72

PhyloP100

0.034

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over