rs17561

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_000575.5(IL1A):c.340G>T(p.Ala114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,604,102 control chromosomes in the GnomAD database, including 67,974 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5330 hom., cov: 32)

Exomes 𝑓: 0.29 ( 62644 hom. )

Consequence

IL1A
NM_000575.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.83

Publications

288 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 -9 ACMG points.

BP6

Variant 2-112779646-C-A is Benign according to our data. Variant chr2-112779646-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060243.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL1A	NM_000575.5	MANE Select	c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	NP_000566.3
	IL1A	NM_001371554.1		c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	NP_001358483.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
IL1A	ENST00000263339.4	TSL:1 MANE Select	c.340G>T	p.Ala114Ser	missense	Exon 5 of 7	ENSP00000263339.3
ENSG00000299339	ENST00000762706.1		n.404+8750C>A		intron	N/A
ENSG00000299339	ENST00000762707.1		n.499+8750C>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.257

AC:

39015

AN:

151936

Hom.:

5326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0797

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.316

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.295

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.270

AC:

67603

AN:

250734

AF XY:

0.275

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.234

Gnomad ASJ exome

AF:

0.340

Gnomad EAS exome

AF:

0.0748

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.301

Gnomad OTH exome

AF:

0.289

GnomAD4 exome

AF:

0.290

AC:

421059

AN:

1452046

Hom.:

62644

Cov.:

AF XY:

0.291

AC XY:

210151

AN XY:

720964

show subpopulations

African (AFR)

AF:

0.177

AC:

5887

AN:

33328

American (AMR)

AF:

0.237

AC:

10572

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8887

AN:

25954

East Asian (EAS)

AF:

0.0896

AC:

3534

AN:

39446

South Asian (SAS)

AF:

0.306

AC:

26292

AN:

85846

European-Finnish (FIN)

AF:

0.315

AC:

16761

AN:

53246

Middle Eastern (MID)

AF:

0.366

AC:

2099

AN:

5740

European-Non Finnish (NFE)

AF:

0.299

AC:

329970

AN:

1103922

Other (OTH)

AF:

0.284

AC:

17057

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

12879

25759

38638

51518

64397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10802

21604

32406

43208

54010

<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:

39041

AN:

152056

Hom.:

5330

Cov.:

AF XY:

0.259

AC XY:

19239

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.180

AC:

7464

AN:

41480

American (AMR)

AF:

0.270

AC:

4129

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3472

East Asian (EAS)

AF:

0.0797

AC:

413

AN:

5180

South Asian (SAS)

AF:

0.298

AC:

1435

AN:

4816

European-Finnish (FIN)

AF:

0.316

AC:

3327

AN:

10544

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.295

AC:

20049

AN:

67970

Other (OTH)

AF:

0.263

AC:

556

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1481

2962

4443

5924

7405

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:

0.279

Hom.:

20541

Bravo

AF:

0.246

TwinsUK

AF:

0.303

AC:

1122

ALSPAC

AF:

0.301

AC:

1161

ESP6500AA

AF:

0.183

AC:

808

ESP6500EA

AF:

0.302

AC:

2595

ExAC

AF:

0.272

AC:

33070

Asia WGS

AF:

0.202

AC:

703

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IL1A-related disorder

Benign:1

Oct 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.067

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

PhyloP100

2.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.081

Sift

Benign

0.20

Sift4G

Uncertain

0.043

Polyphen

0.98

Vest4

0.21

MPC

0.64

ClinPred

0.024

GERP RS

4.4

Varity_R

0.092

gMVP

0.17

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: -11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over