rs4251466

Positions:

• chr12-43770638-C-T

Variant summary

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

The NM_016123.4(IRAK4):​c.162-582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,164 control chromosomes in the GnomAD database, including 1,350 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 0.12 (1350 hom., cov: 32)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK4	NM_016123.4	c.162-582C>T		intron_variant		ENST00000613694.5	NP_057207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK4	ENST00000613694.5	c.162-582C>T		intron_variant		1	NM_016123.4	ENSP00000479889	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18820 AN: 152046 Hom.: 1344 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.0919

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.124 AC: 18846 AN: 152164 Hom.: 1350 Cov.: 32 AF XY: 0.122 AC XY: 9065 AN XY: 74396

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0918

Gnomad4 OTH AF: 0.135

Alfa AF: 0.103 Hom.: 851

Bravo AF: 0.131

Asia WGS AF: 0.122 AC: 423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.46

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: rs4251466; hg19: chr12-44164441;