rs3782347

Variant summary

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

The NM_007199.3(IRAK3):​c.888-6350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,124 control chromosomes in the GnomAD database, including 4,864 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 ( 4864 hom., cov: 31)

Consequence

IRAK3
NM_007199.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.490
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IRAK3NM_007199.3 linkuse as main transcriptc.888-6350A>G intron_variant ENST00000261233.9
IRAK3NM_001142523.2 linkuse as main transcriptc.705-6350A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IRAK3ENST00000261233.9 linkuse as main transcriptc.888-6350A>G intron_variant 1 NM_007199.3 P1Q9Y616-1
IRAK3ENST00000457197.2 linkuse as main transcriptc.705-6350A>G intron_variant 2 Q9Y616-2

Frequencies

GnomAD3 genomes
AF:
0.243
AC:
36942
AN:
152006
Hom.:
4859
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.167
Gnomad AMI
AF:
0.477
Gnomad AMR
AF:
0.258
Gnomad ASJ
AF:
0.298
Gnomad EAS
AF:
0.0631
Gnomad SAS
AF:
0.214
Gnomad FIN
AF:
0.226
Gnomad MID
AF:
0.373
Gnomad NFE
AF:
0.297
Gnomad OTH
AF:
0.278
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.243
AC:
36958
AN:
152124
Hom.:
4864
Cov.:
31
AF XY:
0.240
AC XY:
17848
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.167
Gnomad4 AMR
AF:
0.259
Gnomad4 ASJ
AF:
0.298
Gnomad4 EAS
AF:
0.0627
Gnomad4 SAS
AF:
0.215
Gnomad4 FIN
AF:
0.226
Gnomad4 NFE
AF:
0.297
Gnomad4 OTH
AF:
0.274
Alfa
AF:
0.264
Hom.:
1177
Bravo
AF:
0.241
Asia WGS
AF:
0.141
AC:
490
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
6.9
DANN
Benign
0.80

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: rs3782347; hg19: chr12-66631916; API