IRAK1 p.Gly530Arg

Variant names:

• chrX-154013385-C-G
• NM_001569.4:c.1588G>C
• IRAK1 p.Gly530Arg

Your query was ambiguous. Multiple possible variants found:

• chrX-154013385-C-G
• chrX-154013385-C-T
• chrX-154013383-CCC-ACG
• chrX-154013383-CCC-GCG
• chrX-154013383-CCC-TCG
• chrX-154013383-CCC-TCT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001569.4(IRAK1):​c.1588G>C​(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. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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: 25)
• Consequence: IRAK1 NM_001569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05489421).

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.1588G>C	p.Gly530Arg	missense	Exon 12 of 14	NP_001560.2	P51617-1
	IRAK1	NM_001025243.2		c.1351G>C	p.Gly451Arg	missense	Exon 11 of 13	NP_001020414.1	P51617-4
	IRAK1	NM_001410701.1		c.1618-42G>C		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.1588G>C	p.Gly530Arg	missense	Exon 12 of 14	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000369974.6	TSL:1	c.1351G>C	p.Gly451Arg	missense	Exon 11 of 13	ENSP00000358991.2	P51617-4
	IRAK1	ENST00000393687.6	TSL:1	c.1540-42G>C		intron	N/A	ENSP00000377291.2	P51617-2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.20
DANN	Benign	0.39
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.33
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.12
Sift	Benign	0.35	T
Sift4G	Benign	0.68	T
Varity_R		0.093
gMVP		0.30
Mutation Taster		=96/4	polymorphism

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

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

Other links and lift over

hg19: chrX-153278836;