Variant rs1059703 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001569.4(IRAK1):c.1595C>T(p.Ser532Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.73 ( 22192 hom., 24385 hem., cov: 24)

Exomes 𝑓: 0.80 ( 246066 hom. 281652 hem. )

Failed GnomAD Quality Control

Consequence

IRAK1
NM_001569.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.346

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.4482873E-6).

BP6

Variant X-154013378-G-A is Benign according to our data. Variant chrX-154013378-G-A is described in ClinVar as [Benign]. Clinvar id is 2688071.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAK1	NM_001569.4 linkuse as main transcript	c.1595C>T	p.Ser532Leu	missense_variant	12/14	ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8 linkuse as main transcript	c.1595C>T	p.Ser532Leu	missense_variant	12/14	1	NM_001569.4	ENSP00000358997	P1	P51617-1

Frequencies

GnomAD3 genomes

AF:

0.732

AC:

81784

AN:

111738

Hom.:

22197

Cov.:

AF XY:

0.717

AC XY:

24354

AN XY:

33944

show subpopulations

Gnomad AFR

AF:

0.649

Gnomad AMI

AF:

0.961

Gnomad AMR

AF:

0.569

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.226

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.839

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.849

Gnomad OTH

AF:

0.693

GnomAD3 exomes

AF:

0.674

AC:

110671

AN:

164305

Hom.:

26813

AF XY:

0.681

AC XY:

38591

AN XY:

56707

show subpopulations

Gnomad AFR exome

AF:

0.636

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.753

Gnomad EAS exome

AF:

0.217

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.850

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.800

AC:

870719

AN:

1088268

Hom.:

246066

Cov.:

AF XY:

0.788

AC XY:

281652

AN XY:

357396

show subpopulations

Gnomad4 AFR exome

AF:

0.653

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.750

Gnomad4 EAS exome

AF:

0.235

Gnomad4 SAS exome

AF:

0.418

Gnomad4 FIN exome

AF:

0.844

Gnomad4 NFE exome

AF:

0.865

Gnomad4 OTH exome

AF:

0.744

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.732

AC:

81802

AN:

111794

Hom.:

22192

Cov.:

AF XY:

0.717

AC XY:

24385

AN XY:

34010

show subpopulations

Gnomad4 AFR

AF:

0.648

Gnomad4 AMR

AF:

0.568

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.225

Gnomad4 SAS

AF:

0.376

Gnomad4 FIN

AF:

0.839

Gnomad4 NFE

AF:

0.849

Gnomad4 OTH

AF:

0.693

Alfa

AF:

0.794

Hom.:

12218

Bravo

AF:

0.707

TwinsUK

AF:

0.868

AC:

3220

ALSPAC

AF:

0.869

AC:

2510

ESP6500AA

AF:

0.652

AC:

2477

ESP6500EA

AF:

0.853

AC:

5660

ExAC

AF:

0.681

AC:

82019

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.0

DANN

Benign

0.81

DEOGEN2

Benign

0.043

T;.

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.47

T;T

MetaRNN

Benign

0.0000034

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.55

N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

0.62

N;N

REVEL

Benign

0.12

Sift

Benign

0.30

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;B

Vest4

0.012

MPC

0.42

ClinPred

0.0052

GERP RS

-0.87

BranchPoint Hunter

1.0

Varity_R

0.037

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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