X-154012856-G-A

Variant names:

• chrX-154012856-G-A
• rs763737
• NM_001569.4:c.1931-178C>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.1931-178C>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 (19574 hom., 22647 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 15 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=-0.9).

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.1931-178C>T		intron	N/A	NP_001560.2	P51617-1
	IRAK1	NM_001410701.1		c.1919-178C>T		intron	N/A	NP_001397630.1	D3YTB5
	IRAK1	NM_001025242.2		c.1841-178C>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.1931-178C>T		intron	N/A	ENSP00000358997.3	P51617-1
	IRAK1	ENST00000393687.6	TSL:1	c.1841-178C>T		intron	N/A	ENSP00000377291.2	P51617-2
	IRAK1	ENST00000369974.6	TSL:1	c.1694-178C>T		intron	N/A	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes AF: 0.685 AC: 76359 AN: 111447 Hom.: 19583 Cov.: 24

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.960

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.645

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: 0.685 AC: 76360 AN: 111499 Hom.: 19574 Cov.: 24 AF XY: 0.672 AC XY: 22647 AN XY: 33699

African (AFR) AF: 0.570 AC: 17513 AN: 30731

American (AMR) AF: 0.543 AC: 5782 AN: 10646

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 1951 AN: 2639

East Asian (EAS) AF: 0.213 AC: 750 AN: 3520

South Asian (SAS) AF: 0.368 AC: 989 AN: 2690

European-Finnish (FIN) AF: 0.797 AC: 4783 AN: 5998

Middle Eastern (MID) AF: 0.639 AC: 138 AN: 216

European-Non Finnish (NFE) AF: 0.810 AC: 42832 AN: 52854

Other (OTH) AF: 0.635 AC: 969 AN: 1525

Alfa AF: 0.740 Hom.: 6046

Bravo AF: 0.660

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.016
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

Other links and lift over

dbSNP: rs763737; hg19: chrX-153278307; COSMIC: COSV64110753; COSMIC: COSV64110753;