rs78503618

Positions:

• chr12-66191272-AGGAAGTGGTCAGT-A

Variant summary

Our verdict is Benign. Variant got -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. 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

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 -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/exons	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant		ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant			NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant		1	NM_007199.3	ENSP00000261233.4
IRAK3	ENST00000545837.1	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant		1		ENSP00000441321.1
IRAK3	ENST00000457197.2	c.133+1841_133+1853delGGAAGTGGTCAGT		intron_variant		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

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.223

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78503618; hg19: chr12-66585052;