rs5945174

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-154014407-G-A
• chrX-154014407-G-C

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>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 (19441 hom., 18635 hem., cov: 19)
  • Exomes 𝑓: 0.76 (127142 hom. 121167 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=-0.85).

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

Frequencies

GnomAD3 genomes AF: 0.685 AC: 71954 AN: 105103 Hom.: 19450 Cov.: 19

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.642

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.760 AC: 439062 AN: 578011 Hom.: 127142 Cov.: 9 AF XY: 0.750 AC XY: 121167 AN XY: 161473

African (AFR) AF: 0.595 AC: 7889 AN: 13256

American (AMR) AF: 0.501 AC: 7972 AN: 15901

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 9894 AN: 13566

East Asian (EAS) AF: 0.234 AC: 5535 AN: 23652

South Asian (SAS) AF: 0.435 AC: 14584 AN: 33560

European-Finnish (FIN) AF: 0.811 AC: 27802 AN: 34266

Middle Eastern (MID) AF: 0.616 AC: 1436 AN: 2333

European-Non Finnish (NFE) AF: 0.832 AC: 344129 AN: 413628

Other (OTH) AF: 0.712 AC: 19821 AN: 27849

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.684 AC: 71941 AN: 105106 Hom.: 19441 Cov.: 19 AF XY: 0.664 AC XY: 18635 AN XY: 28054

African (AFR) AF: 0.570 AC: 16386 AN: 28738

American (AMR) AF: 0.539 AC: 5293 AN: 9816

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 1911 AN: 2584

East Asian (EAS) AF: 0.207 AC: 692 AN: 3335

South Asian (SAS) AF: 0.370 AC: 867 AN: 2343

European-Finnish (FIN) AF: 0.773 AC: 3452 AN: 4465

Middle Eastern (MID) AF: 0.622 AC: 125 AN: 201

European-Non Finnish (NFE) AF: 0.809 AC: 41671 AN: 51539

Other (OTH) AF: 0.635 AC: 899 AN: 1416

Alfa AF: 0.611 Hom.: 2706

Bravo AF: 0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.79
PhyloP100		1.2
PromoterAI		-0.0027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;

COSMIC: COSV107477160;

COSMIC: COSV107477160;