rs199501854

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001569.4(IRAK1):c.1798C>T(p.Arg600Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000538 in 1,208,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R600H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., 12 hem., cov: 26)

Exomes 𝑓: 0.000025 ( 0 hom. 9 hem. )

Consequence

IRAK1
NM_001569.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0870

Publications

0 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019124627).

BS2

High Hemizygotes in GnomAd4 at 12 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001569.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAK1	NM_001569.4	MANE Select	c.1798C>T	p.Arg600Cys	missense	Exon 12 of 14	NP_001560.2	P51617-1
IRAK1	NM_001410701.1		c.1786C>T	p.Arg596Cys	missense	Exon 11 of 13	NP_001397630.1	D3YTB5
IRAK1	NM_001025242.2		c.1708C>T	p.Arg570Cys	missense	Exon 12 of 14	NP_001020413.1	P51617-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRAK1	ENST00000369980.8	TSL:1 MANE Select	c.1798C>T	p.Arg600Cys	missense	Exon 12 of 14	ENSP00000358997.3	P51617-1
IRAK1	ENST00000393687.6	TSL:1	c.1708C>T	p.Arg570Cys	missense	Exon 12 of 14	ENSP00000377291.2	P51617-2
IRAK1	ENST00000369974.6	TSL:1	c.1561C>T	p.Arg521Cys	missense	Exon 11 of 13	ENSP00000358991.2	P51617-4

Frequencies

GnomAD3 genomes

AF:

0.000335

AC:

AN:

113523

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000277

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000187

Gnomad OTH

AF:

0.000650

GnomAD2 exomes

AF:

0.0000638

AC:

AN:

172543

AF XY:

0.0000649

show subpopulations

Gnomad AFR exome

AF:

0.000849

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1094847

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

361445

show subpopulations

African (AFR)

AF:

0.000494

AC:

AN:

26325

American (AMR)

AF:

0.0000855

AC:

AN:

35092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19337

East Asian (EAS)

AF:

0.00

AC:

AN:

30087

South Asian (SAS)

AF:

0.00

AC:

AN:

53854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3429

European-Non Finnish (NFE)

AF:

0.00000832

AC:

AN:

841471

Other (OTH)

AF:

0.0000871

AC:

AN:

45934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000335

AC:

AN:

113577

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

35713

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

31362

American (AMR)

AF:

0.000184

AC:

AN:

10883

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.000278

AC:

AN:

3602

South Asian (SAS)

AF:

0.00

AC:

AN:

2849

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

53378

Other (OTH)

AF:

0.000642

AC:

AN:

1557

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00128

Hom.:

Bravo

AF:

0.000378

ESP6500AA

AF:

0.000785

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000661

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.54

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.90

PhyloP100

0.087

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.9

REVEL

Benign

0.15

Sift

Benign

0.14

Sift4G

Benign

0.10

Polyphen

0.0010

Vest4

0.032

MVP

0.62

MPC

0.65

ClinPred

0.038

GERP RS

-0.063

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.090

gMVP

0.17

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over