X-154014407-G-C

Variant names:

• chrX-154014407-G-C
• rs5945174
• NM_001569.4:c.1303-129C>G

Variant summary

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

The NM_001569.4(IRAK1):​c.1303-129C>G 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: not found (cov: 19)
  • Exomes 𝑓: 0.0000017 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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=-0.87).

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.1303-129C>G		intron	N/A	NP_001560.2	P51617-1
	IRAK1	NM_001410701.1		c.1381-129C>G		intron	N/A	NP_001397630.1	D3YTB5
	IRAK1	NM_001025242.2		c.1303-129C>G		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.1303-129C>G		intron	N/A	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000393687.6	TSL:1	c.1303-129C>G		intron	N/A	ENSP00000377291.2	P51617-2
	IRAK1	ENST00000369974.6	TSL:1	c.1303-974C>G		intron	N/A	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000173 AC: 1 AN: 578571 Hom.: 0 Cov.: 9 AF XY: 0.00000619 AC XY: 1 AN XY: 161551

African (AFR) AF: 0.00 AC: 0 AN: 13278

American (AMR) AF: 0.00 AC: 0 AN: 15936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13578

East Asian (EAS) AF: 0.00 AC: 0 AN: 23665

South Asian (SAS) AF: 0.0000298 AC: 1 AN: 33587

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2333

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 414041

Other (OTH) AF: 0.00 AC: 0 AN: 27871

GnomAD4 genome Cov.: 19

Alfa AF: 0.00 Hom.: 2706

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.8
DANN	Benign	0.74
PhyloP100		1.2
PromoterAI		0.0018	Neutral

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: rs5945174;

hg19: chrX-153279858;