chrX-154015024-G-A

Variant names:

• chrX-154015024-G-A
• rs7061789
• NM_001569.4:c.1303-746C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001569.4(IRAK1):​c.1303-746C>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 (19332 hom., 21738 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 13 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.1303-746C>T		intron	N/A	NP_001560.2	P51617-1
	IRAK1	NM_001410701.1		c.1381-746C>T		intron	N/A	NP_001397630.1	D3YTB5
	IRAK1	NM_001025242.2		c.1303-746C>T		intron	N/A	NP_001020413.1	P51617-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1303-746C>T		intron	N/A	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000393687.6	TSL:1	c.1303-746C>T		intron	N/A	ENSP00000377291.2	P51617-2
	IRAK1	ENST00000369974.6	TSL:1	c.1302+1008C>T		intron	N/A	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes AF: 0.680 AC: 75039 AN: 110339 Hom.: 19342 Cov.: 22

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.647

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.640

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.680 AC: 75041 AN: 110391 Hom.: 19332 Cov.: 22 AF XY: 0.666 AC XY: 21738 AN XY: 32659

African (AFR) AF: 0.557 AC: 16893 AN: 30329

American (AMR) AF: 0.536 AC: 5638 AN: 10515

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 1940 AN: 2627

East Asian (EAS) AF: 0.205 AC: 718 AN: 3504

South Asian (SAS) AF: 0.358 AC: 913 AN: 2548

European-Finnish (FIN) AF: 0.795 AC: 4696 AN: 5907

Middle Eastern (MID) AF: 0.636 AC: 136 AN: 214

European-Non Finnish (NFE) AF: 0.809 AC: 42514 AN: 52574

Other (OTH) AF: 0.631 AC: 949 AN: 1504

Alfa AF: 0.730 Hom.: 10469

Bravo AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs7061789; hg19: chrX-153280475;