rs4251513

Variant names:

• chr12-43780401-G-C
• rs4251513
• NM_016123.4:c.942-1906G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016123.4(IRAK4):​c.942-1906G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 151,800 control chromosomes in the GnomAD database, including 30,619 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 0.62 (30619 hom., cov: 29)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550
• Publications: 29 publications found

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]

IRAK4 Gene-Disease associations (from GenCC):

• immunodeficiency 67

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK4	NM_016123.4	c.942-1906G>C		intron_variant	Intron 8 of 11	ENST00000613694.5	NP_057207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK4	ENST00000613694.5	c.942-1906G>C		intron_variant	Intron 8 of 11	1	NM_016123.4	ENSP00000479889.3

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93534 AN: 151682 Hom.: 30573 Cov.: 29

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.632

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.617 AC: 93620 AN: 151800 Hom.: 30619 Cov.: 29 AF XY: 0.619 AC XY: 45900 AN XY: 74164

African (AFR) AF: 0.855 AC: 35423 AN: 41418

American (AMR) AF: 0.540 AC: 8228 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3466

East Asian (EAS) AF: 0.632 AC: 3243 AN: 5130

South Asian (SAS) AF: 0.615 AC: 2956 AN: 4810

European-Finnish (FIN) AF: 0.558 AC: 5866 AN: 10508

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34164 AN: 67908

Other (OTH) AF: 0.589 AC: 1242 AN: 2110

Alfa AF: 0.562 Hom.: 3518

Bravo AF: 0.620

Asia WGS AF: 0.646 AC: 2244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4251513; hg19: chr12-44174204;