12-66248696-G-C

Position:

• chr12-66248696-G-C

Variant summary

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

The NM_007199.3(IRAK3):​c.*525G>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 0.056 in 152,872 control chromosomes in the GnomAD database, including 332 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 0.056 (332 hom., cov: 32)
  • Exomes 𝑓: 0.068 (0 hom.)
• Consequence: IRAK3 NM_007199.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3	c.*525G>C		3_prime_UTR_variant	12/12	ENST00000261233.9
IRAK3	NM_001142523.2	c.*525G>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000261233.9	c.*525G>C		3_prime_UTR_variant	12/12	1	NM_007199.3	P1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8526 AN: 152108 Hom.: 333 Cov.: 32

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0689

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.0560

GnomAD4 exome AF: 0.0681 AC: 44 AN: 646 Hom.: 0 Cov.: 0 AF XY: 0.0533 AC XY: 18 AN XY: 338

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0217

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0667

Gnomad4 NFE exome AF: 0.0758

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.0560 AC: 8522 AN: 152226 Hom.: 332 Cov.: 32 AF XY: 0.0557 AC XY: 4144 AN XY: 74418

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0974

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0687

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0829

Gnomad4 OTH AF: 0.0554

Alfa AF: 0.0662 Hom.: 61

Bravo AF: 0.0527

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.60

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: rs11465990; hg19: chr12-66642476;