chrX-154018721-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001569.4(IRAK1):c.607T>A(p.Cys203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,087,651 control chromosomes in the GnomAD database, including 106 homozygotes. There are 925 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 50 hom., 466 hem., cov: 22)

Exomes 𝑓: 0.0019 ( 56 hom. 459 hem. )

Consequence

IRAK1
NM_001569.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.184

Publications

10 publications found

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 Gene-Disease associations (from GenCC):

systemic lupus erythematosus
Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

IRAK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017255843).

BP6

Variant X-154018721-A-T is Benign according to our data. Variant chrX-154018721-A-T is described in ClinVar as Benign. ClinVar VariationId is 781577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4 link	c.607T>A	p.Cys203Ser	missense_variant	Exon 5 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.607T>A	p.Cys203Ser	missense_variant	Exon 5 of 14	1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.0174

AC:

1915

AN:

109841

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000399

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00844

Gnomad NFE

AF:

0.000152

Gnomad OTH

AF:

0.0130

GnomAD2 exomes

AF:

0.00507

AC:

923

AN:

182162

AF XY:

0.00310

show subpopulations

Gnomad AFR exome

AF:

0.0628

Gnomad AMR exome

AF:

0.00299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000866

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00194

AC:

1899

AN:

977759

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

459

AN XY:

275549

show subpopulations

African (AFR)

AF:

0.0662

AC:

1606

AN:

24276

American (AMR)

AF:

0.00351

AC:

123

AN:

35083

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18662

East Asian (EAS)

AF:

0.00

AC:

AN:

29688

South Asian (SAS)

AF:

0.0000388

AC:

AN:

51592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40313

Middle Eastern (MID)

AF:

0.00182

AC:

AN:

3838

European-Non Finnish (NFE)

AF:

0.0000492

AC:

AN:

732134

Other (OTH)

AF:

0.00296

AC:

125

AN:

42173

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0175

AC:

1921

AN:

109892

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

466

AN XY:

32204

show subpopulations

African (AFR)

AF:

0.0593

AC:

1783

AN:

30047

American (AMR)

AF:

0.0103

AC:

108

AN:

10472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2616

East Asian (EAS)

AF:

0.00

AC:

AN:

3485

South Asian (SAS)

AF:

0.000400

AC:

AN:

2497

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5944

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.000153

AC:

AN:

52452

Other (OTH)

AF:

0.0128

AC:

AN:

1483

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00878

Hom.:

Bravo

AF:

0.0208

ESP6500AA

AF:

0.0660

AC:

253

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00555

AC:

674

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 16, 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

0.068

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.9

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.059

T;.;.;T

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.27

T;T;T;T

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

-0.55

N;N;N;.

PhyloP100

-0.18

PrimateAI

Benign

0.24

PROVEAN

Benign

0.39

N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.74

T;T;T;T

Sift4G

Benign

0.68

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.033

MutPred

0.16

Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);.;

MVP

0.51

MPC

0.59

ClinPred

0.0019

GERP RS

-0.25

PromoterAI

0.0068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.52

Mutation Taster

=93/7

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over