rs1461567

chr12-43770886-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016123.4(IRAK4):c.162-334G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,058 control chromosomes in the GnomAD database, including 4,916 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4916 hom., cov: 31)
• Consequence: IRAK4 NM_016123.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.578

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 12-43770886-G-A is Benign according to our data. Variant chr12-43770886-G-A is described in ClinVar as [Benign]. Clinvar id is 2628208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK4	NM_016123.4	c.162-334G>A		intron_variant		ENST00000613694.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK4	ENST00000613694.5	c.162-334G>A		intron_variant		1	NM_016123.4	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34302 AN: 151940 Hom.: 4913 Cov.: 31

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.234

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

GnomAD4 genome AF: 0.226 AC: 34307 AN: 152058 Hom.: 4916 Cov.: 31 AF XY: 0.234 AC XY: 17397 AN XY: 74326

Gnomad4 AFR AF: 0.0489

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.237

Alfa AF: 0.264 Hom.: 5661

Bravo AF: 0.210

Asia WGS AF: 0.421 AC: 1460 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	2.9
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: rs1461567; hg19: chr12-44164689;