rs17826057

chr12-66239384-G-Achr12-66239384-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.888-5102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 150,780 control chromosomes in the GnomAD database, including 652 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 0.085 (652 hom., cov: 31)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

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 (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3	c.888-5102G>A		intron_variant		ENST00000261233.9
IRAK3	NM_001142523.2	c.705-5102G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000261233.9	c.888-5102G>A		intron_variant		1	NM_007199.3	P1
IRAK3	ENST00000457197.2	c.705-5102G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12853 AN: 150662 Hom.: 653 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.0979

Gnomad ASJ AF: 0.0710

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0754

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0853 AC: 12868 AN: 150780 Hom.: 652 Cov.: 31 AF XY: 0.0874 AC XY: 6424 AN XY: 73474

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.0710

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0883

Gnomad4 NFE AF: 0.0547

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0587 Hom.: 428

Bravo AF: 0.0875

Asia WGS AF: 0.103 AC: 358 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	5.6
Dann	Benign	0.71

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: rs17826057; hg19: chr12-66633164;