rs5945174

chrX-154014407-G-AchrX-154014407-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001569.4(IRAK1):c.1303-129C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.68 (19441 hom., 18635 hem., cov: 19)
  • Exomes 𝑓: 0.76 (127142 hom. 121167 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High Homozygotes in GnomAd at 19450 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRAK1	NM_001569.4	c.1303-129C>T		intron_variant		ENST00000369980.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRAK1	ENST00000369980.8	c.1303-129C>T		intron_variant		1	NM_001569.4	P1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 71954 AN: 105103 Hom.: 19450 Cov.: 19 AF XY: 0.664 AC XY: 18624 AN XY: 28037

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.642

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.760 AC: 439062 AN: 578011 Hom.: 127142 Cov.: 9 AF XY: 0.750 AC XY: 121167 AN XY: 161473

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.501

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.435

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.712

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.684 AC: 71941 AN: 105106 Hom.: 19441 Cov.: 19 AF XY: 0.664 AC XY: 18635 AN XY: 28054

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.740

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.809

Gnomad4 OTH AF: 0.635

Alfa AF: 0.611 Hom.: 2706

Bravo AF: 0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.2
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs5945174; hg19: chrX-153279858;