rs11465955

Variant names:

• chr12-66209619-C-T
• rs11465955
• NM_007199.3:c.381+99C>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.381+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 804,198 control chromosomes in the GnomAD database, including 26,649 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 0.22 (4259 hom., cov: 32)
  • Exomes 𝑓: 0.25 (22390 hom.)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 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.381+99C>T		intron	N/A	NP_009130.2	Q9Y616-1
	IRAK3	NM_001142523.2		c.198+99C>T		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.381+99C>T		intron	N/A	ENSP00000261233.4	Q9Y616-1
	IRAK3	ENST00000854785.1		c.378+99C>T		intron	N/A	ENSP00000524844.1
	IRAK3	ENST00000947373.1		c.381+99C>T		intron	N/A	ENSP00000617432.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33432 AN: 151888 Hom.: 4256 Cov.: 32

Gnomad AFR AF: 0.0904

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.255 AC: 166235 AN: 652192 Hom.: 22390 AF XY: 0.256 AC XY: 90234 AN XY: 351968

African (AFR) AF: 0.0931 AC: 1677 AN: 18018

American (AMR) AF: 0.208 AC: 8518 AN: 40908

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 5944 AN: 20706

East Asian (EAS) AF: 0.136 AC: 4834 AN: 35536

South Asian (SAS) AF: 0.215 AC: 14602 AN: 67956

European-Finnish (FIN) AF: 0.237 AC: 11418 AN: 48226

Middle Eastern (MID) AF: 0.308 AC: 1280 AN: 4152

European-Non Finnish (NFE) AF: 0.285 AC: 109398 AN: 383256

Other (OTH) AF: 0.256 AC: 8564 AN: 33434

GnomAD4 genome AF: 0.220 AC: 33430 AN: 152006 Hom.: 4259 Cov.: 32 AF XY: 0.219 AC XY: 16233 AN XY: 74278

African (AFR) AF: 0.0900 AC: 3732 AN: 41476

American (AMR) AF: 0.248 AC: 3791 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3468

East Asian (EAS) AF: 0.131 AC: 677 AN: 5172

South Asian (SAS) AF: 0.213 AC: 1028 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2426 AN: 10518

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19690 AN: 67950

Other (OTH) AF: 0.263 AC: 554 AN: 2110

Alfa AF: 0.245 Hom.: 644

Bravo AF: 0.215

Asia WGS AF: 0.163 AC: 566 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.42
PhyloP100		-0.77
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: rs11465955; hg19: chr12-66603399; COSMIC: COSV54160254;