X-154017226-C-A

Position:

• chrX-154017226-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001569.4(IRAK1):​c.910-159G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 112,660 control chromosomes in the GnomAD database, including 26 homozygotes. There are 460 hemizygotes in GnomAD. 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 0.015 (26 hom., 460 hem., cov: 24)
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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]

IRAK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0148 (1672/112660) while in subpopulation AFR AF= 0.0513 (1593/31023). AF 95% confidence interval is 0.0493. There are 26 homozygotes in gnomad4. There are 460 alleles in male gnomad4 subpopulation. Median coverage is 24. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 26 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1	NM_001569.4	c.910-159G>T		intron_variant		ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8	c.910-159G>T		intron_variant		1	NM_001569.4	ENSP00000358997.3

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 1661 AN: 112606 Hom.: 26 Cov.: 24 AF XY: 0.0129 AC XY: 450 AN XY: 34754

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00568

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000188

Gnomad OTH AF: 0.00527

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

GnomAD4 genome AF: 0.0148 AC: 1672 AN: 112660 Hom.: 26 Cov.: 24 AF XY: 0.0132 AC XY: 460 AN XY: 34818

Gnomad4 AFR AF: 0.0513

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000188

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0108 Hom.: 19

Bravo AF: 0.0172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.90
DANN	Benign	0.38

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: rs11465835; hg19: chrX-153282677;