chr12-66238136-A-G

Position:

• chr12-66238136-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.888-6350A>G		intron_variant		ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.705-6350A>G		intron_variant			NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.888-6350A>G		intron_variant		1	NM_007199.3	ENSP00000261233	P1
IRAK3	ENST00000457197.2	c.705-6350A>G		intron_variant		2		ENSP00000409852

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

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.274

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

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: rs3782347; hg19: chr12-66631916;