12-43767070-G-C

Position:

• chr12-43767070-G-C

Variant summary

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

The ENST00000613694.5(IRAK4):​c.-9-1033G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,152 control chromosomes in the GnomAD database, including 294 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 0.061 (294 hom., cov: 32)
• Consequence: IRAK4 ENST00000613694.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

Genes affected

IRAK4 (HGNC:17967): (interleukin 1 receptor associated kinase 4) This gene encodes a kinase that activates NF-kappaB in both the Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways. The protein is essential for most innate immune responses. Mutations in this gene result in IRAK4 deficiency and recurrent invasive pneumococcal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK4	NM_016123.4	c.-9-1033G>C		intron_variant		ENST00000613694.5	NP_057207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK4	ENST00000613694.5	c.-9-1033G>C		intron_variant		1	NM_016123.4	ENSP00000479889	P1

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9351 AN: 152034 Hom.: 296 Cov.: 32

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.0604

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0152

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0621

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

GnomAD4 genome AF: 0.0615 AC: 9350 AN: 152152 Hom.: 294 Cov.: 32 AF XY: 0.0598 AC XY: 4447 AN XY: 74380

Gnomad4 AFR AF: 0.0636

Gnomad4 AMR AF: 0.0602

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0347 Hom.: 26

Bravo AF: 0.0633

Asia WGS AF: 0.0180 AC: 62 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.62

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: rs1838341; hg19: chr12-44160873;