12-66224858-T-C

Position:

• chr12-66224858-T-C

Variant summary

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

The ENST00000261233.9(IRAK3):​c.654-1865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 151,942 control chromosomes in the GnomAD database, including 24,878 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 0.55 (24878 hom., cov: 31)
• Consequence: IRAK3 ENST00000261233.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK3	NM_007199.3	c.654-1865T>C		intron_variant		ENST00000261233.9	NP_009130.2
IRAK3	NM_001142523.2	c.471-1865T>C		intron_variant			NP_001135995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK3	ENST00000261233.9	c.654-1865T>C		intron_variant		1	NM_007199.3	ENSP00000261233	P1
IRAK3	ENST00000457197.2	c.471-1865T>C		intron_variant		2		ENSP00000409852

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83546 AN: 151824 Hom.: 24868 Cov.: 31

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.550 AC: 83580 AN: 151942 Hom.: 24878 Cov.: 31 AF XY: 0.554 AC XY: 41138 AN XY: 74258

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.553

Alfa AF: 0.607 Hom.: 7383

Bravo AF: 0.535

Asia WGS AF: 0.558 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.81

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: rs1370128; hg19: chr12-66618638;