rs17561

Variant summary

Our verdict is Benign. Variant got -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. Variant has been reported in ClinVar as Benign (no stars). 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 no assertion criteria provided 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IL1ANM_000575.5 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/7 ENST00000263339.4 NP_000566.3
IL1ANM_001371554.1 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/7 NP_001358483.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IL1AENST00000263339.4 linkuse as main transcriptc.340G>T p.Ala114Ser missense_variant 5/71 NM_000575.5 ENSP00000263339 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: no assertion criteria provided
LINK: link

Submissions by phenotype

IL1A-related disorder Benign:1
Benign, no assertion criteria providedclinical 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