rs78503618

Variant names:

• chr12-66191272-AGGAAGTGGTCAGT-A
• rs78503618
• NM_007199.3:c.133+1841_133+1853delGGAAGTGGTCAGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_007199.3(IRAK3):​c.133+1841_133+1853delGGAAGTGGTCAGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,034 control chromosomes in the GnomAD database, including 4,910 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4910 hom., cov: 23)
• Consequence: IRAK3 NM_007199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.69
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant	Intron 1 of 11	ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant	Intron 1 of 10		NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant	Intron 1 of 11	1	NM_007199.3	ENSP00000261233.4
IRAK3	ENST00000545837.1	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant	Intron 1 of 1	1		ENSP00000441321.1
IRAK3	ENST00000457197.2	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant	Intron 1 of 10	2		ENSP00000409852.2

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37064 AN: 151916 Hom.: 4914 Cov.: 23

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.293

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.244 AC: 37051 AN: 152034 Hom.: 4910 Cov.: 23 AF XY: 0.244 AC XY: 18099 AN XY: 74318

African (AFR) AF: 0.146 AC: 6040 AN: 41492

American (AMR) AF: 0.209 AC: 3189 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1275 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1560 AN: 5146

South Asian (SAS) AF: 0.318 AC: 1531 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2880 AN: 10572

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19917 AN: 67932

Other (OTH) AF: 0.223 AC: 471 AN: 2116

Alfa AF: 0.255 Hom.: 611

Bravo AF: 0.234

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78503618; hg19: chr12-66585052;