Genetic Variant IL1A:c.615+126G>A (chr2-112777861-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.615+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 881,608 control chromosomes in the GnomAD database, including 35,891 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 0.26 ( 5337 hom., cov: 32)

Exomes 𝑓: 0.28 ( 30554 hom. )

Consequence

IL1A
NM_000575.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.81

Publications

15 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=-0.66).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

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.615+126G>A		intron	N/A	NP_000566.3
	IL1A	NM_001371554.1		c.615+126G>A		intron	N/A	NP_001358483.1	P01583

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1A	ENST00000263339.4	TSL:1 MANE Select	c.615+126G>A	intron	N/A	ENSP00000263339.3	P01583
IL1A	ENST00000959423.1		c.615+126G>A	intron	N/A	ENSP00000629482.1
ENSG00000299339	ENST00000762706.1		n.404+6965C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39036

AN:

151946

Hom.:

5333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0795

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.283

AC:

206712

AN:

729544

Hom.:

30554

AF XY:

0.285

AC XY:

107766

AN XY:

378034

show subpopulations

African (AFR)

AF:

0.176

AC:

3138

AN:

17874

American (AMR)

AF:

0.238

AC:

6480

AN:

27216

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

5489

AN:

16204

East Asian (EAS)

AF:

0.0911

AC:

3106

AN:

34082

South Asian (SAS)

AF:

0.305

AC:

16842

AN:

55152

European-Finnish (FIN)

AF:

0.316

AC:

12438

AN:

39326

Middle Eastern (MID)

AF:

0.369

AC:

1509

AN:

4094

European-Non Finnish (NFE)

AF:

0.295

AC:

147704

AN:

500096

Other (OTH)

AF:

0.282

AC:

10006

AN:

35500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7150

14300

21450

28600

35750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3132

6264

9396

12528

15660

<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:

0.257

AC:

39062

AN:

152064

Hom.:

5337

Cov.:

AF XY:

0.259

AC XY:

19266

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.180

AC:

7465

AN:

41484

American (AMR)

AF:

0.270

AC:

4131

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3468

East Asian (EAS)

AF:

0.0795

AC:

412

AN:

5180

South Asian (SAS)

AF:

0.298

AC:

1437

AN:

4826

European-Finnish (FIN)

AF:

0.316

AC:

3339

AN:

10560

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20055

AN:

67940

Other (OTH)

AF:

0.263

AC:

556

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1484

2969

4453

5938

7422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.272

Hom.:

919

Bravo

AF:

0.246

Asia WGS

AF:

0.202

AC:

703

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.49

(source)

DANN

Benign

0.89

PhyloP100

-2.8

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over