rs3027907

Variant names:

• chrX-154013994-A-G
• rs3027907
• NM_001569.4:c.1539+48T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001569.4(IRAK1):​c.1539+48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,178,432 control chromosomes in the GnomAD database, including 835 homozygotes. There are 3,319 hemizygotes in GnomAD. 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 0.058 (443 hom., 1756 hem., cov: 23)
  • Exomes 𝑓: 0.0057 (392 hom. 1563 hem.)
• Consequence: IRAK1 NM_001569.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

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.1539+48T>C		intron	N/A	NP_001560.2
	IRAK1	NM_001410701.1		c.1617+48T>C		intron	N/A	NP_001397630.1
	IRAK1	NM_001025242.2		c.1539+48T>C		intron	N/A	NP_001020413.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1539+48T>C		intron	N/A	ENSP00000358997.3
	IRAK1	ENST00000393687.6	TSL:1	c.1539+48T>C		intron	N/A	ENSP00000377291.2
	IRAK1	ENST00000369974.6	TSL:1	c.1303-561T>C		intron	N/A	ENSP00000358991.2

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 6429 AN: 111943 Hom.: 442 Cov.: 23

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0251

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000368

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.000509

Gnomad OTH AF: 0.0502

GnomAD2 exomes AF: 0.0156 AC: 1968 AN: 126066 AF XY: 0.0106

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.00869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000346

Gnomad OTH exome AF: 0.00702

GnomAD4 exome AF: 0.00573 AC: 6110 AN: 1066439 Hom.: 392 Cov.: 31 AF XY: 0.00453 AC XY: 1563 AN XY: 345289

African (AFR) AF: 0.201 AC: 5005 AN: 24935

American (AMR) AF: 0.0108 AC: 310 AN: 28591

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18599

East Asian (EAS) AF: 0.0000344 AC: 1 AN: 29109

South Asian (SAS) AF: 0.000493 AC: 25 AN: 50694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38242

Middle Eastern (MID) AF: 0.00801 AC: 23 AN: 2870

European-Non Finnish (NFE) AF: 0.000216 AC: 179 AN: 828585

Other (OTH) AF: 0.0127 AC: 567 AN: 44814

GnomAD4 genome AF: 0.0576 AC: 6456 AN: 111993 Hom.: 443 Cov.: 23 AF XY: 0.0513 AC XY: 1756 AN XY: 34245

African (AFR) AF: 0.198 AC: 6082 AN: 30758

American (AMR) AF: 0.0250 AC: 268 AN: 10705

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.000369 AC: 1 AN: 2712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6205

Middle Eastern (MID) AF: 0.00917 AC: 2 AN: 218

European-Non Finnish (NFE) AF: 0.000509 AC: 27 AN: 53012

Other (OTH) AF: 0.0495 AC: 76 AN: 1534

Alfa AF: 0.0464 Hom.: 217

Bravo AF: 0.0676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.40
PhyloP100		0.0
PromoterAI		-0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3027907; hg19: chrX-153279445;