rs4251431

Positions:

• chr12-43760887-G-T

Variant summary

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

The NM_016123.4(IRAK4):​c.-10+1871G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,158 control chromosomes in the GnomAD database, including 1,554 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 (1554 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK4	NM_016123.4	c.-10+1871G>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.-10+1871G>T		intron_variant		1	NM_016123.4	ENSP00000479889.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19771 AN: 151038 Hom.: 1544 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0407

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.131 AC: 19800 AN: 151150 Hom.: 1554 Cov.: 32 AF XY: 0.129 AC XY: 9502 AN XY: 73826

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0914

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0947 Hom.: 695

Bravo AF: 0.140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.36
DANN	Benign	0.083

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: rs4251431; hg19: chr12-44154690;