Variant X-154013332-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001569.4(IRAK1):c.1641C>T(p.Tyr547Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,205,844 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 0 hem., cov: 26)

Exomes 𝑓: 0.000016 ( 0 hom. 9 hem. )

Consequence

IRAK1
NM_001569.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0810

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-154013332-G-A is Benign according to our data. Variant chrX-154013332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037138.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.081 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4 link	c.1641C>T	p.Tyr547Tyr	synonymous_variant	Exon 12 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.1641C>T	p.Tyr547Tyr	synonymous_variant	Exon 12 of 14	1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.00000881

AC:

AN:

113477

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35615

show subpopulations

Gnomad AFR

AF:

0.0000320

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000177

AC:

AN:

169365

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

59493

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000270

Gnomad OTH exome

AF:

0.000236

GnomAD4 exome

AF:

0.0000165

AC:

AN:

1092367

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

359211

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000881

AC:

AN:

113477

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35615

show subpopulations

Gnomad4 AFR

AF:

0.0000320

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000187

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IRAK1-related disorder

Benign:1

May 08, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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