Genetic Variant IL1A:c.320-109A>C (chr2-112779775-T-G) – 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.320-109A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 651,250 control chromosomes in the GnomAD database, including 24,045 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 0.27 ( 5457 hom., cov: 32)

Exomes 𝑓: 0.27 ( 18588 hom. )

Consequence

IL1A
NM_000575.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.342

Publications

18 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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5 link	c.320-109A>C		intron_variant	Intron 4 of 6	ENST00000263339.4	NP_000566.3	P01583
IL1A	NM_001371554.1 link	c.320-109A>C		intron_variant	Intron 4 of 6		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 link	c.320-109A>C		intron_variant	Intron 4 of 6	1	NM_000575.5	ENSP00000263339.3		P01583

Frequencies

GnomAD3 genomes

AF:

0.266

AC:

40414

AN:

152038

Hom.:

5460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.305

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.215

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.269

AC:

134253

AN:

499094

Hom.:

18588

AF XY:

0.270

AC XY:

68323

AN XY:

253312

show subpopulations

African (AFR)

AF:

0.287

AC:

3758

AN:

13076

American (AMR)

AF:

0.190

AC:

3088

AN:

16260

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

3489

AN:

11948

East Asian (EAS)

AF:

0.185

AC:

5239

AN:

28392

South Asian (SAS)

AF:

0.258

AC:

4582

AN:

17734

European-Finnish (FIN)

AF:

0.203

AC:

6256

AN:

30888

Middle Eastern (MID)

AF:

0.222

AC:

401

AN:

1806

European-Non Finnish (NFE)

AF:

0.285

AC:

100857

AN:

353932

Other (OTH)

AF:

0.263

AC:

6583

AN:

25058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

4850

9700

14551

19401

24251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2414

4828

7242

9656

12070

<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:

0.266

AC:

40415

AN:

152156

Hom.:

5457

Cov.:

AF XY:

0.259

AC XY:

19248

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.282

AC:

11687

AN:

41482

American (AMR)

AF:

0.221

AC:

3380

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

967

AN:

3472

East Asian (EAS)

AF:

0.214

AC:

1110

AN:

5184

South Asian (SAS)

AF:

0.240

AC:

1158

AN:

4832

European-Finnish (FIN)

AF:

0.196

AC:

2071

AN:

10590

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19158

AN:

67984

Other (OTH)

AF:

0.253

AC:

534

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1558

3117

4675

6234

7792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.277

Hom.:

863

Bravo

AF:

0.267

Asia WGS

AF:

0.231

AC:

803

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.9

(source)

DANN

Benign

0.58

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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