Variant rs782780153 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001569.4(IRAK1):c.1799G>A(p.Arg600His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,208,587 control chromosomes in the GnomAD database, including 21 homozygotes. There are 724 hemizygotes in GnomAD. 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 (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., 39 hem., cov: 26)

Exomes 𝑓: 0.0012 ( 21 hom. 685 hem. )

Consequence

IRAK1
NM_001569.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.648

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022255778).

BP6

Variant X-154013174-C-T is Benign according to our data. Variant chrX-154013174-C-T is described in ClinVar as [Benign]. Clinvar id is 746901.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000564 (64/113568) while in subpopulation SAS AF= 0.02 (57/2857). AF 95% confidence interval is 0.0158. There are 0 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4 link	c.1799G>A	p.Arg600His	missense_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.1799G>A	p.Arg600His	missense_variant	Exon 12 of 14	1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.000573

AC:

AN:

113515

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

35643

show subpopulations

Gnomad AFR

AF:

0.000128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000553

Gnomad SAS

AF:

0.0202

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00278

AC:

480

AN:

172863

Hom.:

AF XY:

0.00414

AC XY:

256

AN XY:

61849

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000151

Gnomad SAS exome

AF:

0.0252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000397

Gnomad OTH exome

AF:

0.00185

GnomAD4 exome

AF:

0.00118

AC:

1291

AN:

1095019

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

685

AN XY:

361575

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000463

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.000564

AC:

AN:

113568

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

AN XY:

35706

show subpopulations

Gnomad4 AFR

AF:

0.000128

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000555

Gnomad4 SAS

AF:

0.0200

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000189

ExAC

AF:

0.00325

AC:

394

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.015

DANN

Benign

0.81

DEOGEN2

Benign

0.043

T;.;.;T

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.37

T;T;T;T

MetaRNN

Benign

0.0022

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

N;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

0.90

N;N;N;N

REVEL

Benign

0.065

Sift

Benign

0.68

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.018

MutPred

0.24

Loss of phosphorylation at S601 (P = 0.1581);.;.;.;

MVP

0.51

MPC

0.59

ClinPred

0.0035

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.11

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