12-43760604-G-C

Position:

• chr12-43760604-G-C

Variant summary

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

The NM_016123.4(IRAK4):​c.-10+1588G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,190 control chromosomes in the GnomAD database, including 1,852 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 0.099 (1852 hom., cov: 32)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK4	NM_016123.4	c.-10+1588G>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.-10+1588G>C		intron_variant		1	NM_016123.4	ENSP00000479889	P1

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14980 AN: 152072 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.0345

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0986 AC: 15012 AN: 152190 Hom.: 1852 Cov.: 32 AF XY: 0.0969 AC XY: 7209 AN XY: 74406

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.0345

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0107 Hom.: 8

Bravo AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.27
DANN	Benign	0.43

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: rs4251429; hg19: chr12-44154407;