rs2239673

Positions:

• chrX-154012438-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001569.4(IRAK1):​c.2080+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (19454 hom., 22520 hem., cov: 23)
  • Exomes 𝑓: 0.76 (201966 hom. 205319 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.531

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-154012438-C-T is Benign according to our data. Variant chrX-154012438-C-T is described in ClinVar as [Benign]. Clinvar id is 2688217.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1	NM_001569.4	c.2080+91G>A		intron_variant		ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8	c.2080+91G>A		intron_variant		1	NM_001569.4	ENSP00000358997	P1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 76065 AN: 111295 Hom.: 19463 Cov.: 23 AF XY: 0.671 AC XY: 22494 AN XY: 33525

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.643

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.763 AC: 714940 AN: 936515 Hom.: 201966 AF XY: 0.757 AC XY: 205319 AN XY: 271325

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.468

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.412

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.821

Gnomad4 OTH exome AF: 0.707

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.683 AC: 76066 AN: 111350 Hom.: 19454 Cov.: 23 AF XY: 0.670 AC XY: 22520 AN XY: 33590

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.738

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.633

Alfa AF: 0.753 Hom.: 7647

Bravo AF: 0.658

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 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.74

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: rs2239673; hg19: chrX-153277889; COSMIC: COSV64110212; COSMIC: COSV64110212;