rs1152912

Variant names:

• chr12-66240128-A-G
• rs1152912
• NM_007199.3:c.888-4358A>G

Variant summary

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

The NM_007199.3(IRAK3):​c.888-4358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 152,066 control chromosomes in the GnomAD database, including 18,473 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 0.45 (18473 hom., cov: 31)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441
• Publications: 11 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK3	NM_007199.3	MANE Select	c.888-4358A>G		intron	N/A	NP_009130.2	Q9Y616-1
	IRAK3	NM_001142523.2		c.705-4358A>G		intron	N/A	NP_001135995.1	Q9Y616-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK3	ENST00000261233.9	TSL:1 MANE Select	c.888-4358A>G		intron	N/A	ENSP00000261233.4	Q9Y616-1
	IRAK3	ENST00000854785.1		c.885-4358A>G		intron	N/A	ENSP00000524844.1
	IRAK3	ENST00000947373.1		c.834-4358A>G		intron	N/A	ENSP00000617432.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68359 AN: 151948 Hom.: 18481 Cov.: 31

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.449 AC: 68344 AN: 152066 Hom.: 18473 Cov.: 31 AF XY: 0.453 AC XY: 33661 AN XY: 74306

African (AFR) AF: 0.127 AC: 5272 AN: 41514

American (AMR) AF: 0.540 AC: 8260 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1917 AN: 3470

East Asian (EAS) AF: 0.579 AC: 2986 AN: 5156

South Asian (SAS) AF: 0.545 AC: 2628 AN: 4826

European-Finnish (FIN) AF: 0.589 AC: 6216 AN: 10556

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.583 AC: 39610 AN: 67950

Other (OTH) AF: 0.486 AC: 1024 AN: 2106

Alfa AF: 0.548 Hom.: 38959

Bravo AF: 0.433

Asia WGS AF: 0.521 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		0.44
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: rs1152912; hg19: chr12-66633908;