rs1059701

chrX-154019032-G-AchrX-154019032-G-CchrX-154019032-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001569.4(IRAK1):c.483C>T(p.Val161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 111,132 control chromosomes in the GnomAD database, including 16,521 homozygotes. There are 19,637 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (16521 hom., 19637 hem., cov: 23)
  • Exomes 𝑓: 0.75 (216900 hom. 266960 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113

Genes affected

IRAK1 (HGNC:6112): (interleukin 1 receptor associated kinase 1) This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154019032-G-A is Benign according to our data. Variant chrX-154019032-G-A is described in ClinVar as [Benign]. Clinvar id is 2688072.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154019032-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK1	NM_001569.4	c.483C>T	p.Val161=	synonymous_variant	4/14	ENST00000369980.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK1	ENST00000369980.8	c.483C>T	p.Val161=	synonymous_variant	4/14	1	NM_001569.4	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 66610 AN: 111079 Hom.: 16531 Cov.: 23 AF XY: 0.589 AC XY: 19616 AN XY: 33301

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.580

GnomAD3 exomes AF: 0.619 AC: 108720 AN: 175629 Hom.: 24450 AF XY: 0.634 AC XY: 38813 AN XY: 61207

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.212

Gnomad SAS exome AF: 0.412

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.666

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.747 AC: 818552 AN: 1095822 Hom.: 216900 Cov.: 40 AF XY: 0.739 AC XY: 266960 AN XY: 361440

Gnomad4 AFR exome AF: 0.273

Gnomad4 AMR exome AF: 0.443

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.230

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.799

Gnomad4 NFE exome AF: 0.817

Gnomad4 OTH exome AF: 0.683

GnomAD4 genome AF: 0.599 AC: 66601 AN: 111132 Hom.: 16521 Cov.: 23 AF XY: 0.589 AC XY: 19637 AN XY: 33364

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.571

Alfa AF: 0.695 Hom.: 14661

Bravo AF: 0.566

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

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.5
Dann	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1059701; hg19: chrX-153284483; COSMIC: COSV57652578; COSMIC: COSV57652578;