Genetic Variant IL1A:c.*561T>C (chr2-112774506-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.*561T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.256 in 151,728 control chromosomes in the GnomAD database, including 5,310 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 ( 5310 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

IL1A
NM_000575.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.91

Publications

34 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=-0.73).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5 link	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000263339.4	NP_000566.3	P01583
IL1A	NM_001371554.1 link	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 link	c.*561T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_000575.5	ENSP00000263339.3		P01583

Frequencies

GnomAD3 genomes

AF:

0.256

AC:

38870

AN:

151618

Hom.:

5306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0799

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.363

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.264

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.256

AC:

38894

AN:

151728

Hom.:

5310

Cov.:

AF XY:

0.259

AC XY:

19171

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.179

AC:

7429

AN:

41430

American (AMR)

AF:

0.270

AC:

4104

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1190

AN:

3470

East Asian (EAS)

AF:

0.0799

AC:

414

AN:

5184

South Asian (SAS)

AF:

0.298

AC:

1432

AN:

4810

European-Finnish (FIN)

AF:

0.314

AC:

3265

AN:

10412

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.295

AC:

20029

AN:

67896

Other (OTH)

AF:

0.263

AC:

553

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1509

3019

4528

6038

7547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.273

Hom.:

3563

Bravo

AF:

0.246

Asia WGS

AF:

0.201

AC:

699

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

3.9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over