chrX-154013383-CCC-ACG

Variant names:

• chrX-154013383-CCC-ACG
• NM_001569.4:c.1588_1590delGGGinsCGT
• IRAK1 p.Gly530Arg

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001569.4(IRAK1):​c.1588_1590delGGGinsCGT​(p.Gly530Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: IRAK1 NM_001569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	NM_001569.4	MANE Select	c.1588_1590delGGGinsCGT	p.Gly530Arg	missense	N/A	NP_001560.2	P51617-1
	IRAK1	NM_001025243.2		c.1351_1353delGGGinsCGT	p.Gly451Arg	missense	N/A	NP_001020414.1	P51617-4
	IRAK1	NM_001410701.1		c.1618-42_1618-40delGGGinsCGT		intron	N/A	NP_001397630.1	D3YTB5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1588_1590delGGGinsCGT	p.Gly530Arg	missense	N/A	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000369974.6	TSL:1	c.1351_1353delGGGinsCGT	p.Gly451Arg	missense	N/A	ENSP00000358991.2	P51617-4
	IRAK1	ENST00000393687.6	TSL:1	c.1540-42_1540-40delGGGinsCGT		intron	N/A	ENSP00000377291.2	P51617-2

Frequencies

GnomAD3 genomes Cov.: 24

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

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-153278834;