rs1732886

Variant names:

• chr12-66189982-G-A
• rs1732886
• NM_007199.3:c.133+550G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-66189982-G-A
• chr12-66189982-G-C
• chr12-66189982-G-T

Variant summary

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

The NM_007199.3(IRAK3):​c.133+550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,098 control chromosomes in the GnomAD database, including 44,032 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 0.75 (44032 hom., cov: 32)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• Publications: 10 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.133+550G>A		intron_variant	Intron 1 of 11	ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.133+550G>A		intron_variant	Intron 1 of 10		NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.133+550G>A		intron_variant	Intron 1 of 11	1	NM_007199.3	ENSP00000261233.4
IRAK3	ENST00000545837.1	c.133+550G>A		intron_variant	Intron 1 of 1	1		ENSP00000441321.1
IRAK3	ENST00000457197.2	c.133+550G>A		intron_variant	Intron 1 of 10	2		ENSP00000409852.2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114620 AN: 151978 Hom.: 43985 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.783

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.734

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

GnomAD4 genome AF: 0.754 AC: 114723 AN: 152098 Hom.: 44032 Cov.: 32 AF XY: 0.753 AC XY: 55957 AN XY: 74346

African (AFR) AF: 0.881 AC: 36596 AN: 41522

American (AMR) AF: 0.620 AC: 9470 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2689 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4568 AN: 5168

South Asian (SAS) AF: 0.760 AC: 3666 AN: 4826

European-Finnish (FIN) AF: 0.670 AC: 7072 AN: 10548

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48139 AN: 67976

Other (OTH) AF: 0.733 AC: 1549 AN: 2114

Alfa AF: 0.733 Hom.: 16734

Bravo AF: 0.754

Asia WGS AF: 0.804 AC: 2797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.65
PhyloP100		0.60
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: rs1732886; hg19: chr12-66583762;