rs1882200

Positions:

• chr12-66203921-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007199.3(IRAK3):​c.316+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 1,573,750 control chromosomes in the GnomAD database, including 58,478 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 0.24 (4755 hom., cov: 32)
  • Exomes 𝑓: 0.27 (53723 hom.)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3	c.316+28C>T		intron_variant		ENST00000261233.9
IRAK3	NM_001142523.2	c.134-5535C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000261233.9	c.316+28C>T		intron_variant		1	NM_007199.3	P1
IRAK3	ENST00000457197.2	c.134-5535C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36749 AN: 151990 Hom.: 4749 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.276

GnomAD3 exomes AF: 0.242 AC: 60704 AN: 250596 Hom.: 7972 AF XY: 0.247 AC XY: 33503 AN XY: 135456

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.200

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.212

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.270 AC: 384296 AN: 1421642 Hom.: 53723 Cov.: 25 AF XY: 0.270 AC XY: 191648 AN XY: 709792

Gnomad4 AFR exome AF: 0.169

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.287

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.242 AC: 36773 AN: 152108 Hom.: 4755 Cov.: 32 AF XY: 0.239 AC XY: 17798 AN XY: 74358

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.273

Alfa AF: 0.257 Hom.: 1407

Bravo AF: 0.239

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs1882200; hg19: chr12-66597701; COSMIC: COSV54160242;