rs1624395

chr12-66224436-A-Gchr12-66224436-A-T

Variant summary

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

The NM_007199.3(IRAK3):c.654-2287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,016 control chromosomes in the GnomAD database, including 30,415 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 0.63 (30415 hom., cov: 31)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK3	NM_007199.3	c.654-2287A>G		intron_variant		ENST00000261233.9
IRAK3	NM_001142523.2	c.471-2287A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK3	ENST00000261233.9	c.654-2287A>G		intron_variant		1	NM_007199.3	P1
IRAK3	ENST00000457197.2	c.471-2287A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95561 AN: 151900 Hom.: 30381 Cov.: 31

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.629 AC: 95642 AN: 152016 Hom.: 30415 Cov.: 31 AF XY: 0.631 AC XY: 46893 AN XY: 74306

Gnomad4 AFR AF: 0.562

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.612

Alfa AF: 0.649 Hom.: 8767

Bravo AF: 0.623

Asia WGS AF: 0.574 AC: 2000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.34
Dann	Benign	0.77

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: rs1624395; hg19: chr12-66618216;