rs1059701

Variant names:

• chrX-154019032-G-A
• rs1059701
• NM_001569.4:c.483C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-154019032-G-A
• chrX-154019032-G-C
• chrX-154019032-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001569.4(IRAK1):​c.483C>T​(p.Val161Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 111,132 control chromosomes in the GnomAD database, including 16,521 homozygotes. There are 19,637 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (16521 hom., 19637 hem., cov: 23)
  • Exomes 𝑓: 0.75 (216900 hom. 266960 hem.)
  • Failed GnomAD Quality Control
• Consequence: IRAK1 NM_001569.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.113
• Publications: 27 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant X-154019032-G-A is Benign according to our data. Variant chrX-154019032-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.113 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4	c.483C>T	p.Val161Val	synonymous_variant	Exon 4 of 14	ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8	c.483C>T	p.Val161Val	synonymous_variant	Exon 4 of 14	1	NM_001569.4	ENSP00000358997.3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 66610 AN: 111079 Hom.: 16531 Cov.: 23

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.629

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.580

GnomAD2 exomes AF: 0.619 AC: 108720 AN: 175629 AF XY: 0.634

Gnomad AFR exome AF: 0.274

Gnomad AMR exome AF: 0.437

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.792

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.666

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.747 AC: 818552 AN: 1095822 Hom.: 216900 Cov.: 40 AF XY: 0.739 AC XY: 266960 AN XY: 361440

African (AFR) AF: 0.273 AC: 7202 AN: 26360

American (AMR) AF: 0.443 AC: 15388 AN: 34711

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 13815 AN: 19277

East Asian (EAS) AF: 0.230 AC: 6926 AN: 30157

South Asian (SAS) AF: 0.417 AC: 22436 AN: 53836

European-Finnish (FIN) AF: 0.799 AC: 32282 AN: 40406

Middle Eastern (MID) AF: 0.574 AC: 2355 AN: 4102

European-Non Finnish (NFE) AF: 0.817 AC: 686722 AN: 840985

Other (OTH) AF: 0.683 AC: 31426 AN: 45988

GnomAD4 genome AF: 0.599 AC: 66601 AN: 111132 Hom.: 16521 Cov.: 23 AF XY: 0.589 AC XY: 19637 AN XY: 33364

African (AFR) AF: 0.285 AC: 8739 AN: 30662

American (AMR) AF: 0.514 AC: 5428 AN: 10565

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 1943 AN: 2634

East Asian (EAS) AF: 0.217 AC: 761 AN: 3510

South Asian (SAS) AF: 0.367 AC: 978 AN: 2666

European-Finnish (FIN) AF: 0.792 AC: 4737 AN: 5978

Middle Eastern (MID) AF: 0.616 AC: 133 AN: 216

European-Non Finnish (NFE) AF: 0.804 AC: 42367 AN: 52710

Other (OTH) AF: 0.571 AC: 866 AN: 1516

Alfa AF: 0.694 Hom.: 17713

Bravo AF: 0.566

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		0.11
PromoterAI		-0.021	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1059701; hg19: chrX-153284483; COSMIC: COSV57652578; COSMIC: COSV57652578;