rs11465955

Positions:

• chr12-66209619-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.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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.381+99C>T		intron_variant		ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.198+99C>T		intron_variant			NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.381+99C>T		intron_variant		1	NM_007199.3	ENSP00000261233	P1
IRAK3	ENST00000457197.2	c.198+99C>T		intron_variant		2		ENSP00000409852

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

Gnomad4 AFR exome AF: 0.0931

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.136

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.256

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

Gnomad4 AFR AF: 0.0900

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.263

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.42

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: rs11465955; hg19: chr12-66603399; COSMIC: COSV54160254;