rs4251520

chr12-43781535-T-C

Variant summary

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

The NM_016123.4(IRAK4):c.942-772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,248 control chromosomes in the GnomAD database, including 1,424 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 0.13 (1424 hom., cov: 32)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK4	NM_016123.4	c.942-772T>C		intron_variant		ENST00000613694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK4	ENST00000613694.5	c.942-772T>C		intron_variant		1	NM_016123.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19644 AN: 152130 Hom.: 1423 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0863

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.129 AC: 19651 AN: 152248 Hom.: 1424 Cov.: 32 AF XY: 0.128 AC XY: 9539 AN XY: 74438

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.0850

Gnomad4 ASJ AF: 0.0863

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.112

Alfa AF: 0.116 Hom.: 1430

Bravo AF: 0.127

Asia WGS AF: 0.0340 AC: 121 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.6
Dann	Benign	0.55

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: rs4251520; hg19: chr12-44175338;