Genetic Variant IL1A:c.320-96T>C (chr2-112779762-A-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.320-96T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 764,626 control chromosomes in the GnomAD database, including 27,518 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 0.24 ( 5004 hom., cov: 32)

Exomes 𝑓: 0.26 ( 22514 hom. )

Consequence

IL1A
NM_000575.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

Publications

9 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:

Genome browser will be placed here

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 (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5 link	c.320-96T>C		intron_variant	Intron 4 of 6	ENST00000263339.4	NP_000566.3
IL1A	NM_001371554.1 link	c.320-96T>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.320-96T>C		intron_variant	Intron 4 of 6	1	NM_000575.5	ENSP00000263339.3

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36785

AN:

152036

Hom.:

5004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0798

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.255

GnomAD4 exome

AF:

0.264

AC:

161751

AN:

612472

Hom.:

22514

AF XY:

0.268

AC XY:

83092

AN XY:

310360

show subpopulations

African (AFR)

AF:

0.118

AC:

1860

AN:

15802

American (AMR)

AF:

0.236

AC:

5043

AN:

21398

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

4470

AN:

13286

East Asian (EAS)

AF:

0.0927

AC:

2829

AN:

30524

South Asian (SAS)

AF:

0.297

AC:

7551

AN:

25408

European-Finnish (FIN)

AF:

0.313

AC:

10945

AN:

34954

Middle Eastern (MID)

AF:

0.330

AC:

692

AN:

2100

European-Non Finnish (NFE)

AF:

0.274

AC:

120662

AN:

439880

Other (OTH)

AF:

0.264

AC:

7699

AN:

29120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

5515

11029

16544

22058

27573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3084

6168

9252

12336

15420

<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:

0.242

AC:

36790

AN:

152154

Hom.:

5004

Cov.:

AF XY:

0.244

AC XY:

18168

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.128

AC:

5304

AN:

41508

American (AMR)

AF:

0.264

AC:

4045

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1189

AN:

3468

East Asian (EAS)

AF:

0.0798

AC:

413

AN:

5178

South Asian (SAS)

AF:

0.297

AC:

1434

AN:

4824

European-Finnish (FIN)

AF:

0.316

AC:

3344

AN:

10584

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20047

AN:

67980

Other (OTH)

AF:

0.254

AC:

535

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1387

2774

4160

5547

6934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.261

Hom.:

881

Bravo

AF:

0.229

Asia WGS

AF:

0.197

AC:

685

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

1.5

(source)

DANN

Benign

0.70

PhyloP100

0.20

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