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GeneBe

rs17561

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.26 ( 5330 hom., cov: 32)
Exomes 𝑓: 0.29 ( 62644 hom. )

Consequence

IL1A
NM_000575.5 missense

Scores

2
16

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.83
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 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 id is 3060243.Status of the report is criteria_provided_single_submitter, 1 stars.
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/exons MANE UniProt
IL1ANM_000575.5 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/7 ENST00000263339.4
IL1ANM_001371554.1 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL1AENST00000263339.4 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/71 NM_000575.5 P1

Frequencies

GnomAD3 genomes
AF:
0.257
AC:
39015
AN:
151936
Hom.:
5326
Cov.:
32
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
GnomAD3 exomes
AF:
0.270
AC:
67603
AN:
250734
Hom.:
9650
AF XY:
0.275
AC XY:
37261
AN XY:
135534
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 SAS exome
AF:
0.308
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.:
32
AF XY:
0.291
AC XY:
210151
AN XY:
720964
show subpopulations
Gnomad4 AFR exome
AF:
0.177
Gnomad4 AMR exome
AF:
0.237
Gnomad4 ASJ exome
AF:
0.342
Gnomad4 EAS exome
AF:
0.0896
Gnomad4 SAS exome
AF:
0.306
Gnomad4 FIN exome
AF:
0.315
Gnomad4 NFE exome
AF:
0.299
Gnomad4 OTH exome
AF:
0.284
GnomAD4 genome
AF:
0.257
AC:
39041
AN:
152056
Hom.:
5330
Cov.:
32
AF XY:
0.259
AC XY:
19239
AN XY:
74292
show subpopulations
Gnomad4 AFR
AF:
0.180
Gnomad4 AMR
AF:
0.270
Gnomad4 ASJ
AF:
0.343
Gnomad4 EAS
AF:
0.0797
Gnomad4 SAS
AF:
0.298
Gnomad4 FIN
AF:
0.316
Gnomad4 NFE
AF:
0.295
Gnomad4 OTH
AF:
0.263
Alfa
AF:
0.285
Hom.:
15188
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: criteria provided, single submitter
LINK: link

Submissions by phenotype

IL1A-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 22, 2019This 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 v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.69
Cadd
Benign
22
Dann
Uncertain
0.99
DEOGEN2
Benign
0.17
T
Eigen
Benign
-0.067
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.73
T
MetaRNN
Benign
0.0056
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.081
Sift
Benign
0.20
T
Sift4G
Uncertain
0.043
D
Polyphen
0.98
D
Vest4
0.21
MPC
0.64
ClinPred
0.024
T
GERP RS
4.4
Varity_R
0.092
gMVP
0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17561; hg19: chr2-113537223; COSMIC: COSV54518892; API