rs10506481

chr12-66250331-T-C

Variant summary

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

The NM_007199.3(IRAK3):c.*2160T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0897 in 152,256 control chromosomes in the GnomAD database, including 658 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 0.090 (658 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: IRAK3 NM_007199.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3	c.*2160T>C		3_prime_UTR_variant	12/12	ENST00000261233.9
IRAK3	NM_001142523.2	c.*2160T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000261233.9	c.*2160T>C		3_prime_UTR_variant	12/12	1	NM_007199.3	P1

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13645 AN: 152136 Hom.: 655 Cov.: 32

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.0954

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0843

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0883

Gnomad OTH AF: 0.0827

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.0897 AC: 13660 AN: 152254 Hom.: 658 Cov.: 32 AF XY: 0.0888 AC XY: 6610 AN XY: 74454

Gnomad4 AFR AF: 0.0907

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0843

Gnomad4 NFE AF: 0.0883

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0909 Hom.: 163

Bravo AF: 0.0911

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.31
Dann	Benign	0.43

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: rs10506481; hg19: chr12-66644111;