Variant chr12-66196952-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000545837.1(IRAK3):c.206A>G(p.Tyr69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,535,268 control chromosomes in the GnomAD database, including 2,335 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.071 ( 1244 hom., cov: 32)

Exomes 𝑓: 0.0077 ( 1091 hom. )

Consequence

IRAK3
ENST00000545837.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

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 links:

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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 (MetaRNN=0.0020825267).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3 linkuse as main transcript	c.134-6759A>G		intron_variant		ENST00000261233.9
IRAK3	NM_001142523.2 linkuse as main transcript	c.133+7520A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000545837.1 linkuse as main transcript	c.206A>G	p.Tyr69Cys	missense_variant	2/2	1
IRAK3	ENST00000261233.9 linkuse as main transcript	c.134-6759A>G		intron_variant		1	NM_007199.3	P1	Q9Y616-1
IRAK3	ENST00000457197.2 linkuse as main transcript	c.133+7520A>G		intron_variant		2			Q9Y616-2

Frequencies

GnomAD3 genomes

AF:

0.0709

AC:

10782

AN:

152120

Hom.:

1243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0297

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0147

AC:

1967

AN:

133466

Hom.:

211

AF XY:

0.0115

AC XY:

838

AN XY:

72690

show subpopulations

Gnomad AFR exome

AF:

0.237

Gnomad AMR exome

AF:

0.0127

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000449

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00150

Gnomad OTH exome

AF:

0.0129

GnomAD4 exome

AF:

0.00771

AC:

10669

AN:

1383030

Hom.:

1091

Cov.:

AF XY:

0.00684

AC XY:

4671

AN XY:

682422

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0165

Gnomad4 ASJ exome

AF:

0.00135

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000772

Gnomad4 FIN exome

AF:

0.0000590

Gnomad4 NFE exome

AF:

0.000942

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0709

AC:

10797

AN:

152238

Hom.:

1244

Cov.:

AF XY:

0.0679

AC XY:

5055

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0296

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0133

Hom.:

189

Bravo

AF:

0.0822

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0115

AC:

172

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.53

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Uncertain

-4.4

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Polyphen

1.0

Vest4

0.13

ClinPred

0.088

GERP RS

4.4

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over