dbSNP rs1059701: IRAK1:p.Val161Val (chrX-154019032-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.113

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 2688072.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154019032-G-A is described in Lovd as [Likely_benign].

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 link	c.483C>T	p.Val161Val	synonymous_variant	Exon 4 of 14	ENST00000369980.8	NP_001560.2	P51617-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8 link	c.483C>T	p.Val161Val	synonymous_variant	Exon 4 of 14	1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

66610

AN:

111079

Hom.:

16531

Cov.:

AF XY:

0.589

AC XY:

19616

AN XY:

33301

show subpopulations

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

GnomAD3 exomes

AF:

0.619

AC:

108720

AN:

175629

Hom.:

24450

AF XY:

0.634

AC XY:

38813

AN XY:

61207

show subpopulations

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 SAS exome

AF:

0.412

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.:

AF XY:

0.739

AC XY:

266960

AN XY:

361440

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.443

Gnomad4 ASJ exome

AF:

0.717

Gnomad4 EAS exome

AF:

0.230

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.799

Gnomad4 NFE exome

AF:

0.817

Gnomad4 OTH exome

AF:

0.683

GnomAD4 genome

AF:

0.599

AC:

66601

AN:

111132

Hom.:

16521

Cov.:

AF XY:

0.589

AC XY:

19637

AN XY:

33364

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.367

Gnomad4 FIN

AF:

0.792

Gnomad4 NFE

AF:

0.804

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.695

Hom.:

14661

Bravo

AF:

0.566

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over