rs1882200

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007199.3(IRAK3):​c.316+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,573,750 control chromosomes in the GnomAD database, including 58,478 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 0.24 ( 4755 hom., cov: 32)
Exomes 𝑓: 0.27 ( 53723 hom. )

Consequence

IRAK3
NM_007199.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273
Variant links:
Genes affected
IRAK3 (HGNC:17020): (interleukin 1 receptor associated kinase 3) This gene encodes a member of the interleukin-1 receptor-associated kinase protein family. Members of this family are essential components of the Toll/IL-R immune signal transduction pathways. This protein is primarily expressed in monocytes and macrophages and functions as a negative regulator of Toll-like receptor signaling. Mutations in this gene are associated with a susceptibility to asthma. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRAK3NM_007199.3 linkuse as main transcriptc.316+28C>T intron_variant ENST00000261233.9
IRAK3NM_001142523.2 linkuse as main transcriptc.134-5535C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRAK3ENST00000261233.9 linkuse as main transcriptc.316+28C>T intron_variant 1 NM_007199.3 P1Q9Y616-1
IRAK3ENST00000457197.2 linkuse as main transcriptc.134-5535C>T intron_variant 2 Q9Y616-2

Frequencies

GnomAD3 genomes
AF:
0.242
AC:
36749
AN:
151990
Hom.:
4749
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.167
Gnomad AMI
AF:
0.470
Gnomad AMR
AF:
0.254
Gnomad ASJ
AF:
0.289
Gnomad EAS
AF:
0.129
Gnomad SAS
AF:
0.214
Gnomad FIN
AF:
0.229
Gnomad MID
AF:
0.364
Gnomad NFE
AF:
0.290
Gnomad OTH
AF:
0.276
GnomAD3 exomes
AF:
0.242
AC:
60704
AN:
250596
Hom.:
7972
AF XY:
0.247
AC XY:
33503
AN XY:
135456
show subpopulations
Gnomad AFR exome
AF:
0.166
Gnomad AMR exome
AF:
0.200
Gnomad ASJ exome
AF:
0.284
Gnomad EAS exome
AF:
0.129
Gnomad SAS exome
AF:
0.212
Gnomad FIN exome
AF:
0.236
Gnomad NFE exome
AF:
0.289
Gnomad OTH exome
AF:
0.266
GnomAD4 exome
AF:
0.270
AC:
384296
AN:
1421642
Hom.:
53723
Cov.:
25
AF XY:
0.270
AC XY:
191648
AN XY:
709792
show subpopulations
Gnomad4 AFR exome
AF:
0.169
Gnomad4 AMR exome
AF:
0.210
Gnomad4 ASJ exome
AF:
0.285
Gnomad4 EAS exome
AF:
0.135
Gnomad4 SAS exome
AF:
0.213
Gnomad4 FIN exome
AF:
0.236
Gnomad4 NFE exome
AF:
0.287
Gnomad4 OTH exome
AF:
0.264
GnomAD4 genome
AF:
0.242
AC:
36773
AN:
152108
Hom.:
4755
Cov.:
32
AF XY:
0.239
AC XY:
17798
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.167
Gnomad4 AMR
AF:
0.254
Gnomad4 ASJ
AF:
0.289
Gnomad4 EAS
AF:
0.129
Gnomad4 SAS
AF:
0.215
Gnomad4 FIN
AF:
0.229
Gnomad4 NFE
AF:
0.290
Gnomad4 OTH
AF:
0.273
Alfa
AF:
0.257
Hom.:
1407
Bravo
AF:
0.239
Asia WGS
AF:
0.173
AC:
603
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
13
DANN
Benign
0.75

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

LitVar

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

Other links and lift over

dbSNP: rs1882200; hg19: chr12-66597701; COSMIC: COSV54160242; API