Genetic Variant NM_000575.5:c.*408A>G (chr2-112774659-T-C) – 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.*408A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 157,704 control chromosomes in the GnomAD database, including 8,122 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 ( 7899 hom., cov: 31)

Exomes 𝑓: 0.26 ( 223 hom. )

Consequence

IL1A
NM_000575.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.343

Publications

25 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 (AFR) allele frequency at 95% confidence interval = 0.382 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.*408A>G		3_prime_UTR	Exon 7 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.*408A>G		3_prime_UTR	Exon 7 of 7	NP_001358483.1	P01583

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IL1A	ENST00000263339.4	TSL:1 MANE Select	c.*408A>G	3_prime_UTR	Exon 7 of 7	ENSP00000263339.3	P01583
IL1A	ENST00000959423.1		c.*408A>G	3_prime_UTR	Exon 6 of 6	ENSP00000629482.1
ENSG00000299339	ENST00000762706.1		n.404+3763T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47933

AN:

151676

Hom.:

7876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.387

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.0790

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.314

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.257

AC:

1519

AN:

5914

Hom.:

223

Cov.:

AF XY:

0.256

AC XY:

804

AN XY:

3142

show subpopulations

African (AFR)

AF:

0.344

AC:

AN:

American (AMR)

AF:

0.239

AC:

287

AN:

1202

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

AN:

East Asian (EAS)

AF:

0.0663

AC:

AN:

362

South Asian (SAS)

AF:

0.293

AC:

167

AN:

570

European-Finnish (FIN)

AF:

0.224

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.272

AC:

898

AN:

3298

Other (OTH)

AF:

0.309

AC:

AN:

220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

117

175

234

292

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.316

AC:

47999

AN:

151790

Hom.:

7899

Cov.:

AF XY:

0.316

AC XY:

23422

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.387

AC:

16017

AN:

41356

American (AMR)

AF:

0.291

AC:

4441

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1191

AN:

3466

East Asian (EAS)

AF:

0.0790

AC:

408

AN:

5164

South Asian (SAS)

AF:

0.301

AC:

1448

AN:

4816

European-Finnish (FIN)

AF:

0.314

AC:

3294

AN:

10498

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.296

AC:

20074

AN:

67920

Other (OTH)

AF:

0.306

AC:

645

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1620

3241

4861

6482

8102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.311

Hom.:

2251

Bravo

AF:

0.315

Asia WGS

AF:

0.214

AC:

747

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Benign

0.85

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over