12-66239384-G-A

Variant names:

• chr12-66239384-G-A
• rs17826057
• NM_007199.3:c.888-5102G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007199.3(IRAK3):​c.888-5102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 150,780 control chromosomes in the GnomAD database, including 652 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 0.085 (652 hom., cov: 31)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 6 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK3	NM_007199.3	MANE Select	c.888-5102G>A		intron	N/A	NP_009130.2
	IRAK3	NM_001142523.2		c.705-5102G>A		intron	N/A	NP_001135995.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK3	ENST00000261233.9	TSL:1 MANE Select	c.888-5102G>A		intron	N/A	ENSP00000261233.4
	IRAK3	ENST00000457197.2	TSL:2	c.705-5102G>A		intron	N/A	ENSP00000409852.2

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12853 AN: 150662 Hom.: 653 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0754

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0853 AC: 12868 AN: 150780 Hom.: 652 Cov.: 31 AF XY: 0.0874 AC XY: 6424 AN XY: 73474

African (AFR) AF: 0.132 AC: 5423 AN: 41088

American (AMR) AF: 0.0979 AC: 1479 AN: 15108

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 246 AN: 3466

East Asian (EAS) AF: 0.0815 AC: 416 AN: 5106

South Asian (SAS) AF: 0.0927 AC: 445 AN: 4800

European-Finnish (FIN) AF: 0.0883 AC: 891 AN: 10096

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3712 AN: 67822

Other (OTH) AF: 0.0766 AC: 160 AN: 2090

Alfa AF: 0.0616 Hom.: 1006

Bravo AF: 0.0875

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17826057; hg19: chr12-66633164;