rs3782347

Variant names:

• chr12-66238136-A-G
• rs3782347
• NM_007199.3:c.888-6350A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007199.3(IRAK3):​c.888-6350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,124 control chromosomes in the GnomAD database, including 4,864 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 0.24 (4864 hom., cov: 31)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 7 publications found

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]

IRAK3 Gene-Disease associations (from GenCC):

• asthma-related traits, susceptibility to, 5

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.888-6350A>G		intron_variant	Intron 8 of 11	ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.705-6350A>G		intron_variant	Intron 7 of 10		NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.888-6350A>G		intron_variant	Intron 8 of 11	1	NM_007199.3	ENSP00000261233.4
IRAK3	ENST00000457197.2	c.705-6350A>G		intron_variant	Intron 7 of 10	2		ENSP00000409852.2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36942 AN: 152006 Hom.: 4859 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.243 AC: 36958 AN: 152124 Hom.: 4864 Cov.: 31 AF XY: 0.240 AC XY: 17848 AN XY: 74364

African (AFR) AF: 0.167 AC: 6916 AN: 41500

American (AMR) AF: 0.259 AC: 3952 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1033 AN: 3470

East Asian (EAS) AF: 0.0627 AC: 325 AN: 5184

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4824

European-Finnish (FIN) AF: 0.226 AC: 2393 AN: 10574

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20185 AN: 67984

Other (OTH) AF: 0.274 AC: 577 AN: 2106

Alfa AF: 0.264 Hom.: 1177

Bravo AF: 0.241

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.9
DANN	Benign	0.80
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3782347; hg19: chr12-66631916;