dbSNP rs3027898: IRAK1:c.*1420G>T (chrX-154010439-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001569.4(IRAK1):c.*1420G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 6,095 control chromosomes in the GnomAD database, including 1,151 homozygotes. There are 915 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 19380 hom., 21574 hem., cov: 22)

Exomes 𝑓: 0.66 ( 1151 hom. 915 hem. )

Failed GnomAD Quality Control

Consequence

IRAK1
NM_001569.4 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.392

Publications

63 publications found

Variant links:

COSMIC-nc: COSV64110208

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4 link	c.*1420G>T		downstream_gene_variant		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.*1420G>T		downstream_gene_variant		1	NM_001569.4	ENSP00000358997.3		P51617-1

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

75018

AN:

109876

Hom.:

19389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.570

Gnomad AMI

AF:

0.960

Gnomad AMR

AF:

0.543

Gnomad ASJ

AF:

0.739

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.793

Gnomad MID

AF:

0.650

Gnomad NFE

AF:

0.805

Gnomad OTH

AF:

0.647

GnomAD4 exome

AF:

0.655

AC:

3994

AN:

6095

Hom.:

1151

AF XY:

0.673

AC XY:

915

AN XY:

1359

show subpopulations

African (AFR)

AF:

0.496

AC:

AN:

119

American (AMR)

AF:

0.483

AC:

556

AN:

1151

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.209

AC:

120

AN:

574

South Asian (SAS)

AF:

0.364

AC:

152

AN:

418

European-Finnish (FIN)

AF:

0.819

AC:

362

AN:

442

Middle Eastern (MID)

AF:

0.286

AC:

AN:

European-Non Finnish (NFE)

AF:

0.820

AC:

2525

AN:

3080

Other (OTH)

AF:

0.708

AC:

170

AN:

240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

133

178

222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<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

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.682

AC:

75019

AN:

109924

Hom.:

19380

Cov.:

AF XY:

0.669

AC XY:

21574

AN XY:

32238

show subpopulations

African (AFR)

AF:

0.570

AC:

17194

AN:

30180

American (AMR)

AF:

0.542

AC:

5584

AN:

10309

Ashkenazi Jewish (ASJ)

AF:

0.739

AC:

1938

AN:

2622

East Asian (EAS)

AF:

0.212

AC:

738

AN:

3481

South Asian (SAS)

AF:

0.360

AC:

933

AN:

2595

European-Finnish (FIN)

AF:

0.793

AC:

4558

AN:

5751

Middle Eastern (MID)

AF:

0.638

AC:

136

AN:

213

European-Non Finnish (NFE)

AF:

0.805

AC:

42326

AN:

52586

Other (OTH)

AF:

0.637

AC:

963

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

758

1516

2275

3033

3791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.738

Hom.:

44042

Bravo

AF:

0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.88

(source)

DANN

Benign

0.73

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over