rs2239673

Variant names:

• chrX-154012438-C-T
• rs2239673
• NM_001569.4:c.2080+91G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001569.4(IRAK1):​c.2080+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (19454 hom., 22520 hem., cov: 23)
  • Exomes 𝑓: 0.76 (201966 hom. 205319 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.531
• Publications: 10 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-154012438-C-T is Benign according to our data. Variant chrX-154012438-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688217.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2080+91G>A		intron	N/A	NP_001560.2	P51617-1
	IRAK1	NM_001410701.1		c.2068+91G>A		intron	N/A	NP_001397630.1	D3YTB5
	IRAK1	NM_001025242.2		c.1990+91G>A		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.2080+91G>A		intron	N/A	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000393687.6	TSL:1	c.1990+91G>A		intron	N/A	ENSP00000377291.2	P51617-2
	IRAK1	ENST00000369974.6	TSL:1	c.1843+91G>A		intron	N/A	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 76065 AN: 111295 Hom.: 19463 Cov.: 23

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.653

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.643

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.763 AC: 714940 AN: 936515 Hom.: 201966 AF XY: 0.757 AC XY: 205319 AN XY: 271325

African (AFR) AF: 0.582 AC: 12830 AN: 22035

American (AMR) AF: 0.468 AC: 10908 AN: 23308

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 10197 AN: 14215

East Asian (EAS) AF: 0.229 AC: 6483 AN: 28268

South Asian (SAS) AF: 0.412 AC: 17032 AN: 41353

European-Finnish (FIN) AF: 0.823 AC: 25941 AN: 31529

Middle Eastern (MID) AF: 0.610 AC: 1450 AN: 2378

European-Non Finnish (NFE) AF: 0.821 AC: 601931 AN: 733565

Other (OTH) AF: 0.707 AC: 28168 AN: 39864

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.683 AC: 76066 AN: 111350 Hom.: 19454 Cov.: 23 AF XY: 0.670 AC XY: 22520 AN XY: 33590

African (AFR) AF: 0.569 AC: 17403 AN: 30604

American (AMR) AF: 0.543 AC: 5746 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 1951 AN: 2645

East Asian (EAS) AF: 0.213 AC: 746 AN: 3503

South Asian (SAS) AF: 0.360 AC: 977 AN: 2712

European-Finnish (FIN) AF: 0.810 AC: 4815 AN: 5946

Middle Eastern (MID) AF: 0.642 AC: 140 AN: 218

European-Non Finnish (NFE) AF: 0.806 AC: 42673 AN: 52938

Other (OTH) AF: 0.633 AC: 962 AN: 1520

Alfa AF: 0.753 Hom.: 7647

Bravo AF: 0.658

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.74
PhyloP100		-0.53
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: rs2239673;

hg19: chrX-153277889;

COSMIC: COSV64110212;

COSMIC: COSV64110212;