dbSNP rs11465990: IRAK3:c.*525G>C (chr12-66248696-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007199.3(IRAK3):c.*525G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 152,872 control chromosomes in the GnomAD database, including 332 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 0.056 ( 332 hom., cov: 32)

Exomes 𝑓: 0.068 ( 0 hom. )

Consequence

IRAK3
NM_007199.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

Publications

10 publications found

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]

IRAK3 Gene-Disease associations (from GenCC):

asthma-related traits, susceptibility to, 5
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

IRAK3 links:

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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK3	NM_007199.3 link	c.*525G>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000261233.9	NP_009130.2	Q9Y616-1
IRAK3	NM_001142523.2 link	c.*525G>C		3_prime_UTR_variant	Exon 11 of 11		NP_001135995.1	Q9Y616-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9 link	c.*525G>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_007199.3	ENSP00000261233.4		Q9Y616-1

Frequencies

GnomAD3 genomes

AF:

0.0561

AC:

8526

AN:

152108

Hom.:

333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0974

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0689

Gnomad FIN

AF:

0.0680

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0829

Gnomad OTH

AF:

0.0560

GnomAD4 exome

AF:

0.0681

AC:

AN:

646

Hom.:

Cov.:

AF XY:

0.0533

AC XY:

AN XY:

338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0217

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0667

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0758

AC:

AN:

462

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0560

AC:

8522

AN:

152226

Hom.:

332

Cov.:

AF XY:

0.0557

AC XY:

4144

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.0143

AC:

595

AN:

41538

American (AMR)

AF:

0.0466

AC:

713

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0974

AC:

338

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5178

South Asian (SAS)

AF:

0.0687

AC:

332

AN:

4832

European-Finnish (FIN)

AF:

0.0680

AC:

720

AN:

10586

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0829

AC:

5636

AN:

68016

Other (OTH)

AF:

0.0554

AC:

117

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

427

854

1280

1707

2134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0662

Hom.:

Bravo

AF:

0.0527

Asia WGS

AF:

0.0330

AC:

113

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.46

(source)

DANN

Benign

0.60

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs11465990

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over