Genetic Variant NM_000575.5: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL1A	NM_000575.5 link	c.615+126G>A		intron_variant	Intron 6 of 6	ENST00000263339.4	NP_000566.3	P01583
IL1A	NM_001371554.1 link	c.615+126G>A		intron_variant	Intron 6 of 6		NP_001358483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL1A	ENST00000263339.4 link	c.615+126G>A		intron_variant	Intron 6 of 6	1	NM_000575.5	ENSP00000263339.3		P01583

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over