NM_000575.5:c.615+126G>A

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

2

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]

Genome browser will be placed here

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
IL1ANM_000575.5 linkc.615+126G>A intron_variant Intron 6 of 6 ENST00000263339.4 NP_000566.3 P01583
IL1ANM_001371554.1 linkc.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
IL1AENST00000263339.4 linkc.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.:
32
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
0
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
0
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.:
32
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
0
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
0
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
DANN
Benign
0.89
PhyloP100
-2.8
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071375; hg19: chr2-113535438; API